Integrative and Comparative Biology Advance Access published May 2, 2014

Integrative and Comparative Biology

Integrative and Comparative Biology, pp. 113
doi:10.1093/icb/icu029

Society for Integrative and Comparative Biology

SYMPOSIUM

Cellular Respiration: The Nexus of Stress, Condition,

and Ornamentation
Geoffrey E. Hill1
Department of Biological Sciences, 331 Funchess Hall, Auburn University, Auburn, AL 36849-5414, USA

E-mail: ghill@auburn.edu

Synopsis A fundamental hypothesis for the evolution and maintenance of ornamental traits is that ornaments convey
information to choosing females about the quality of prospective mates. A diverse array of ornaments (e.g., colors,
morphological features, and behaviors) has been associated with a wide range of measures of individual quality, but
decades of study of such indicator traits have failed to produce general mechanisms of honest signaling. Here, I propose
that efficiency of cellular respiration, as a product of mitochondrial function, underlies the associations between ornamentation and performance for a broad range of traits across taxa. A large biomedical literature documents the fundamental biochemical links between oxidative phosphorylation (OXPHOS) and the production of reactive oxygen species
(ROS), the process of metabolism, the function of the immune system, the synthesis of proteins, and the development
and function of the nervous system. The production of virtually all ornaments whose expressions have been demonstrated
to be condition-dependent is directly affected by the efficiency of cellular respiration, suggesting that the signaling of
respiratory efficiency may be the primary function of such traits. Furthermore, the production of ornaments links to
stress-response systems, including particularly the neuroendocrine system, through mitochondrial function, thereby
makes ornamental traits effective signals of the capacity to withstand environmental perturbations. The identification
of a unifying mechanism of honest signaling holds the potential to connect many heretofore-disparate fields of study
related to stress and ornamentation, including neuroendocrinology, respiratory physiology, metabolic physiology, and
immunology.

Introduction
For more than three decades, behavioral, evolutionary, and physiological ecologists have been fascinated
by the idea that the quality of an ornamental display
might signal key information about an individuals
condition (Zahavi 1975; Kodric-Brown and Brown
1984; Andersson 1994; Mller 1994; Hill 2002;
Warren et al. 2013). Many studies have shown
links between ornamentation and various measures
of conditon, including recovery from, and resistance
to, parasites (Mller 1994; Lindstrom and Lundstrom
2000; Roulin et al. 2001; Hill and Farmer 2005), immunocompetence (Reid et al. 2005; Mougeot 2008),
oxidative state (Perez-Rodrguez et al. 2010), capacity
to survive an epidemic (Nolan et al. 1998; Van Oort
and Dawson 2005), moderation of stress-response
(Douglas et al. 2009; Almasi et al. 2010), cognition

and problem-solving (Keagy et al. 2011; MateosGonzalez et al. 2011), and quality of sperm (Peters
et al. 2004; Helfenstein et al. 2010; Navara et al.
2012). Despite this focused interest, studies of condition-dependent signaling lack coherency (Warren
et al. 2013).
The failure to uncover general mechanisms linking
ornamentation to individual condition is at least in
part a consequence of the lack of a clear and comprehensive definition of the concept of condition. In
a recent essay, I proposed condition to be the functionality of vital cellular processes such that A
condition-dependent display trait is a conspicuous
feature of an organism that varies in expression depending on the capacity to withstand environmental
challenges (Hill 2011). These definitions help to
clarify what is meant by the concept of condition

The Author 2014. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved.
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From the symposium Stress, Condition and Ornamentation presented at the annual meeting of the Society for
Integrative and Comparative Biology, January 37, 2014 at Austin, Texas.

and how ornamentation can serve as a signal of condition, but they retain significant ambiguities regarding which of many vital cellular pathways potentially
underlie the execution of ornamentation. Here, I further clarify the concept of condition by proposing
that the core cellular process that determines the
condition of animals is cellular respiration. I propose
that most condition-dependent ornaments are signals
of the efficiency of cellular respiration and that cellular respiration links stress-response systems, particularly the neuroendocrine system, to the production
of ornamental traits.

The hypothesis that cellular respiration is the fundamental biochemical process signaled by ornaments
provides a testable hypothesis for the mechanistic
basis for condition-dependency and honest signaling.
For this hypothesis to be an accurate description
of natural systems, three key assumptions must be
met: First, within populations, individuals must
vary in their efficiency of cellular respiration.
Mitochondrial functionality, which dictates respiratory efficiency, is a result both of intrinsic and of
extrinsic factors (Burton et al. 2013; Pereira et al.
2014). Intrinsic effects on cellular respiration arise
from genetic interactions that are independent of
the extra-organismal environment. In contrast, extrinsic effects on cellular respiration arise from impacts of the environment on mitochondrial function.
There is abundant evidence from model systems
studied in laboratory environments that intrinsic effects, and especially mitochondrialnuclear genetic
interactions, can generate within-population variation in mitochondrial function (Frank and Hurst
1996; Gemmell et al. 2004) including the functionality of cellular respiration (McKenzie et al. 2003;
Smith et al. 2010; Pereira et al. 2014). The few studies that have examined cellular respiration in wild
animals indicate that there is also substantial variation in natural populations, with important effects
on organisms performance (Salin et al. 2010, 2012).
A second key assumption is that mitochondrial
function can be affected by environmental perturbations. In other words, extrinsic effects on mitochondrial function can lead to variation in respiratory
efficiency (Pereira et al. 2014). The effects of a
wide range of stressors on mitochondrial function
and the central role that mitochondria play in
stressresponsiveness are focal topics in the biomedical literature (e.g., Manoli et al. 2007) but have been
largely unexplored within the realm of wild animals
responding to environmental challenges. Much of

this article will focus on reviewing the mechanisms

that link environmental stressors to mitochondrial
function.
Finally, the third critical assumption is that efficiency of cellular respiration affects the production
of condition-dependent ornaments. The central
premise of this hypothesis is that a choosing female
cannot directly assess the cellular respiration of a
prospective mate. Ornaments evolve as conspicuous,
easily perceived, and assessed signals of the efficiency
of cellular respiration. I spend the last sections of this
article reviewing available evidence that ornamentation signals the efficiency of cellular respiration.
The hypothesis that I propose is that a vital lifeprocess underlies honest signaling in a diversity of
ornaments. The identification of such a unifying
mechanism holds the potential to connect fields of
study related to stress and ornamentation, including
neuroendocrinology, respiratory physiology, metabolic physiology, and immunology.

Cellular respirationthe core

life-process in animals
Life persists by capturing energy from the environment and using energy to organize molecules into
more copies of itself (Lane 2010). Energy both enables and constrains life. For animals, energy is made
available for life-processes via respirationthe slow
combustion of carbohydrates, fats, and proteins
through which the chemical energy in food is captured in ATP (adenosine triphosphate) or released as
heat (Shutt and McBride 2013). Aerobic respiration
involves three metabolic steps: glycolysis, the Krebs
cycle, and oxidative phosphorylation (OXPHOS).
Glycolysis occurs in the cytosol; the Krebs cycle
takes place in the matrix of the mitochondria;
OXPHOS occurs via the electron-transport chain
and is carried out on the inner mitochondrial membrane. The efficiency of cellular respiration determines the number of ATP molecules derived from
each unit of food, as well as the number of harmful
free radicals that are created by the respiratory process (Brand 2005; Lane 2011a; Shutt and McBride
2013).
In this article, I focus primarily on the final stage
in the respiratory process, the production of ATP
by OXPHOS via the electron-transport system.
OXPHOS is of special interest with regard to stress,
condition, and ornamentation because: (1) it is the
part of the respiratory process in which 90% of
oxygen is consumed and from which most ATP is
produced (Lane 2005; Wallace 2008), (2) it is the
source of most of the free radicals that create the

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Testable assumptions

G. E. Hill

Cellular respiration and condition

Fig. 1 A conceptual framework for the mechanistic connections

between stress, condition, and ornamentation. Cellular respiration/mitochondrial function determine the condition of an individual. The efficiency of cellular respiration is a product of the
somatic state of an animal as influenced by genotype and epigenotype. Stressors can also have a significant impact on somatic
state and, in turn, on cellular respiration. The outcome of the
efficiency of cellular respiration is the performance of the animal
and the ability to produce ornaments. A choosing female can
predict future performance by assessing the ornamentation of
a prospective mate. Adapted from Hill (2011).

the neuroendocrine stress axis, and cognition are

united in their close association with the process of
OXPHOS and mitochondrial function. In this article
I review the evidence for links between conventional
measures of condition and mitochondrial function
and discuss the implications of the hypothesis that
cellular respiration is the nexus of condition, stress,
and ornamentation (Fig. 1).

Mitochondrial function, efficiency

of OXPHOS, and mitonuclear
compatibility
The emergence and evolution of eukaryotes involved
the chimeric union of two genomes now recognized
as the nuclear and mitochondrial genomes (Dyall
et al. 2004; Lane 2005). Even though these genomes
likely began with approximately equal numbers of
genes, the great majority of mitochondrial genes
(mt genes) migrated to the nuclear genome, leaving
only 34 mt genes in vertebrate animals (Lane 2005;
Wallace 2007). Mitochondrial processes, however, are
extremely complex and multifarious and involve the
products of more then 1500 genes (Lopez et al.
2000). Thus, many nuclear genes produce proteins
that are expressed in the mitochondria (N-mt
genes). Proper functioning of the mitochondria, including efficient OXPHOS, requires both the appropriate production and function of N-mt genes and
the appropriate production and function of mt genes
(Calvo and Mootha 2010). In addition, the products

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oxidative state of an animal (Barja 2007; Lane 2011a;

2011b; Murphy 2009), (3) it is under regulatory control by retinoids (Hill and Johnson 2012) and glucocorticoids (Lee et al. 2013; Scheller and Sekeris
2013), (4) it is intimately linked to the synthesis of
proteins (Lane and Martin 2010) and to the folding
and maintenance of proteins (Simmen et al. 2010),
and (5) it is dependent on the compatibility of products from mitochondrial and nuclear genes (Lane
2011a; Bar-Yaacov et al. 2012).
Approximately 90% of ATP is produced from
OXPHOS via the transfer of electrons along the electron transport chain from a donor such as NADH to
oxygen as the terminal acceptor (Lane 2005). This
flow of electrons powers the pumping of protons
across the inner mitochondrial membrane, establishing the membrane potential that ultimately leads to
production of ATP from ADP. Efficient production
of ATP depends on availability of oxygen and on
an unimpeded flow of electrons along the electron
transport chain (Lane 2011a). If there are structural
problems with the complexes of the electron transport chain then the flow of electrons along the chain
is impeded, leading to decreased output of ATP and
increased leakage of free radicals (Murphy 2009).
The release of cytochrome C under such conditions
of poor OXPHOS performance can trigger apoptosis
and the removal of cells that have compromised respiration (Hengartner 1998). Efficient respiration depends critically not only on the functional integrity
of electron transport complexes, but also on the
match between respiratory capacity, electron donors,
and electron receivers (Brand and Nicholls 2011;
Lane 2011a). If capacity is too low for the electron
donors, the result is wasted energy and an increased
production of free radicals (Barja 2007). In this case,
free radicals play a critical role as signaling molecules
(Droge 2002), initiating the up-regulation of genes
that code for respiratory capacity (Lane 2011a).
Efficiency of cellular respiration is not simply a maximization of ATP production; rather, efficiency describes the matching of the output of energy to the
need for energy, with minimal production of free
radicals (Brand and Nicholls 2011; Lane 2011a).
The proposition that indicator traits signal the
functionality of OXPHOS is inherently attractive because the fundamental premise of indicator traits has
always been that they signal core aspects of an individuals quality (Kodric-Brown and Brown 1984;
Zahavi 1975). Cellular respiration via OXPHOS lies
at the very heart of eukaryotic function (Lane and
Martin 2010; Wallace and Fan 2010). Numerous, apparently unrelated components of condition such as
immunocompetence, oxidative state, energy reserves,

Stress, condition, and cellular

respiration
Cellular respiration and oxidative stress
Along with ATP, the primary product of OXPHOS is
reactive oxygen species (ROS). In general, production of less ROS is indicative of a well functioning
electron transport chain (Murphy 2009; Lane 2011a).
However, production of some ROS is critical for
proper system function because ROS serve as key
signaling molecules, regulating mitochondrial function (Mittler et al. 2011). Mitochondria also are primarily responsible for oxidative stress-responses that
enable increased release of free radicals for defense
against invaders and for signaling (Apel and Hirt
2004), or that lead to reduced release of free radicals,
thereby protecting vital tissues (Foyer and Noctor
2005).
The molecular structure of cells, including proteins, nucleic acids, and lipids, can be damaged by
the redox reactions that are initiated by ROS. The
body neutralizes free radicals by employing a host of
antioxidants that are both endogenously produced or
derived from diet that can either donate or receive

electrons without becoming reactive molecules themselves (Radak et al. 2013). von Schantz et al. (1999)
first articulated the hypothesis that ornamentation is
a signal of individual condition because production
of ornaments is sensitive to oxidative stress.
Although von Schantz et al. did not focus on tradeoffs, other biologists interested in honest signaling
related to oxidative stress have proposed that production of ornaments diverts antioxidants away from
the bodys protective mechanisms (Aguilera and
Amat 2007; Alonso-Alvarez et al. 2007; Costantini
2008). Hence, it is proposed that individuals subject
to lower oxidative stress have more resources of antioxidant to use for production of ornaments, whereas individuals with higher oxidative stress have fewer
resources (McGraw et al. 2010).
An alternative to the resource-allocation hypothesis is the shared-pathway hypothesis whereby the
mechanisms of production of ornaments share functional pathways with core life-supporting pathways,
such that ornamentation cannot be fully produced
unless core life-supporting pathways are fully functional (Hill 2011). By this hypothesis, the link between the oxidative state of an animal and
ornamentation is the functionality of cellular respiration. Mitochondrial dysfunction leading to increased release of free radicals also leads to reduced
capacity for production of ornaments because ornament production depends on efficient mitochondrial
function (Hill and Johnson 2013; Johnson and Hill
2013). I propose that it is not a tradeoff of
resourcesbe they antioxidants, ATP molecules,
lipids, or any other currencybut rather the pathways shared between ornament production and
cellular respiration that is the basis for the persistent associations between oxidative state and
ornamentation.
Stressors and the stress-response
In the physiological literature, there is a variable and
somewhat inconsistent use of the terms stress and
stressor (Buchanan 2000; Romero et al. 2009).
Biologists commonly use the term stress to describe both the physiological response to a stressor
as well as the stress-response itself (Romero et al.
2009). In this review, I will generally avoid the
term stress except in general contexts when ambiguity is acceptable, and instead use the less ambiguous terms stressor and stress-response. I
consider a stressor to be an environmental perturbation that disrupts the functionality of the organism (sensu Badyaev 2005; Hill 2011), whereas a

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of some N-mt genes form complexes with, or interact in important ways with, the products of mt
genes, and there must be close coordination of
these interacting genetic systems (hereafter called
mitonuclear compatibility) for full functionality
of mitochondrial systems (Blier et al. 2001).
Mitochondrial and nuclear components of these protein complexes not only must fit and function together, they must also be produced in stoichiometric
proportions (i.e., there must be mitonuclear protein
balance) (Woodson and Chory 2008; Hootkooper
et al. 2013). Mitonuclear protein imbalance leads to
reduced cellular respiration and triggers an unfolded
protein response, a classic stress-response mechanism
(Wu and Kaufman 2006; Mandl et al. 2013).
In this article, when I refer to poor mitochondrial
function (mitochondrial dysfunction), I mean poor
performance of the cellular and biochemical processes that are known to take place within mitochondria (Manoli et al. 2007). Mitochondrial dysfunction
will include poor performance of OXPHOS, because
this is a core mitochondrial process, but it will also
include other biochemical processes carried out by
mitochondria. Mitochondrial dysfunction can also
relate to the number, size, and distribution of mitochondria within cells and across regions of the body
(Duchen 2004). When there are specific ties to
OXPHOS, I will refer to OXPHOS function rather
than to mitochondrial function.

G. E. Hill

Cellular respiration and condition

The stress axis, immune-response, and

mitochondrial function
Hormonal control of mitochondrial function
The stress-response of vertebrates commonly is discussed within the context of the neuroendocrine

mechanisms involved in extra-cellular signaling

(Wingfield et al. 1998; Buchanan 2000; Husak and
Moore 2008). Indeed, the hypothalamicpituitary
adrenal (HPA) axis is termed the stress axis
(Herman and Cullinan 1997; Romero 2004). One
of the primary outcomes of vertebrates stressresponse is a change in immune responsiveness
(Segerstrom and Miller 2004), and it has been proposed and widely discussed that condition-dependent
ornamental traits are signals of immunocompetence
(Hamilton and Zuk 1982; Folstad and Karter 1992;
Westneat and Birkhead 1998). Hence, the honesty of
ornamental signals often is proposed to emerge
either from the cost of immune suppression that
arises when testosterone is increased to stimulate
the production of ornaments (Folstad and Karter
1992) or from tradeoffs in the use of immuneenhancing elements for ornamentation versus maintenance (Alonso-Alvarez et al. 2007, 2009). In such
discussions of stress, condition, immunocompetence,
and ornamentation, the missing linchpin is cellular
respiration and mitochondrial function.
Mitochondria are among the primary sites of
action of the steroid and thyroid hormones
(Koufali et al. 2003; Psarra et al. 2006; Du et al.
2009; Lee et al. 2013). They primarily are responsible
for meeting the energy demands of a stress-response
by oxidizing energy-storing molecules that are mobilized from energy stores. Thus, stress hormones
might be viewed as regulators of mitochondrial processes (Psarra and Sekeris 2009) and particularly
OXPHOS (Scheller and Sekeris 2013); such that the
links between stress hormones and system function
play out through mitochondrial processes (Fig. 2).
Stressors can have a direct effect on mitochondrial
function and hence on cellular respiration. Indeed, a
stress-response is largely a mitochondrial response
(Manoli et al. 2007; Shutt and McBride 2013), and
mitochondria employ a range of mechanisms, often
under regulation of stress hormones, in response to
stress (Manoli et al. 2007) including: (1) modifying
the production of energy, (2) making more mitochondria in targeted tissue thereby providing greater
respiratory capacity (Jornayvaz and Shulman 2010),
(3) mediating rate of transcriptionregulation both
of mitochondrial and nuclear subunits of electrontransport complexes that control respiratory capacity
(Psarra et al. 2006), (4) fever response (Mackowiak
1998), (5) controlling signal transduction to the nucleus and other organelles that coordinate whole-cell
responses (Hamanaka and Chandel 2010), (6) generating ROS for signaling and defense (Underhill and
Ozinsky 2002; Lambeth 2004), (7) regulating innate
immune-responses (Arnoult et al. 2011; West et al.

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stress-response refers to the physiological responses

brought about by a stressor (Buchanan 2000).
The overarching concept of stress is intimately
linked to condition. Indeed, the signaling function
of indicator traits is proposed to be the capacity
to withstand environmental challenges (Hill 2011).
Stressors are proposed to impact an individuals condition and hence its ornamentation, while condition
mediates the effects of an environmental stressor on
system function (Fig. 1). Thus, two inter-related aspects of an individual are potentially signaled via
condition-dependent ornamentation: (1) functionality under normal, non-stressful conditions and (2)
functionality under duress caused by a stressor. The
most useful ornaments will be those in which expression under optimal conditions indicates functionality
under duress.
To make the point of the value of conditiondependent ornaments that signal integrity of systems
under duress, an analogy can be drawn between financial systems and biological systems. Both are
highly complex with inputs of resources, pathways
through which resources are modified and repackaged, and end-products that contribute to the fitness
(biological or economic) of the entity. The recent
financial crisis that beset banks, in which a drop in
the value of real estate acted as a powerful stressor
on financial systems, could be thought of as analogous to the environmental perturbations that sometimes beset organisms. In the face of a poor market
environment some banks failed, some survived in a
seriously compromised state, and a few flourished. In
other words, some had a higher capacity to maintain
functionality of their system while under duress,
while others did not. How useful would it have
been for investors to have had honest signals of the
quality of the internal systems of these financial institutions? If banks and investment firms had published uncheatable and easily perceived signals of the
systems integrity, such signals would obviously have
been closely monitored by individuals choosing a
bank in which to invest. Indicator traits are proposed
to evolve as just such uncheatable and easily perceived signals of system-integrity (Kodric-Brown
and Brown 1984), and I propose that they do so
because ornamentation is intimately linked to cellular respiration (Fig. 1).

2011), and (8) regulating apoptosis of cells in affected tissues (Arnoult et al. 2009; Ohta and
Nishiyama 2011). Each of these stress-responses is
intimately related to cellular respiration.
Hormones affect mitochondrial function through
action on nuclear and mitochondrial gene transcription (Psarra et al. 2006; Scheller and Sekeris 2013).
Glucocorticoid receptors are present in mitochondria
and the mitochondrial genome has elements of glucocorticoid response, suggesting that mitochondrial
genes are under direct glucocorticoid control (Lee
et al. 2013). Thus, it appears that mitochondrial
function can be regulated by glucocorticoids either
via direct action on mitochondrial OXPHOS genes
or by indirect effects through interaction with nuclear genes that code for OXPHOS complexes (Lee
et al. 2013).
Innate immunity and mitochondrial function
There are also direct connections between cellular
respiration and immune-system response, and the
metabolic control of immunity is a fast-growing
field (Moore et al. 2008; West et al. 2011; Strowig
et al. 2012). Mitochondrial bioenergetics is tightly
linked to innate immunity and to the overall

immune-response (Lartigue and Faustin 2013).

Mitochondria first gained attention as key regulators
of innate immunity with the discovery of mitochondrial antiviral signaling protein (MAVS) (Seth et al.
2005), which plays a key role in recognition of viruses and activates a cascade of innate-response
mechanisms. Subsequently, mitochondria were
shown also to play a key role in bacterial defense
(West et al. 2011). It is now well established that
mitochondria sit at the core of innate immune signaling and are the primary effectors of immuneresponses (Arnoult et al. 2011; West et al. 2011;
Cloonan and Choi 2012).
Arnoult et al. (2011) proposed that by serving as
the center of multiple pathways for innate immunity
as well as for production both of ATP and ROS,
mitochondria could coordinate tight functional integration of host-defense and metabolic processes.
Moreover, functional coupling of innate immunity
and mitochondria would ensure that efficient cellintrinsic defense pathways involving release of ROS
would only be activated in cells with appropriate
mitochondrial membrane potential and oxidative
state. These recent studies linking immune defense
to mitochondrial function and cellular respiration
provide an intriguing explanation for the often-observed associations between ornamentation, immunocompetence, and the oxidative state of wild
animals (reviewed by Simons et al. 2012).
Mitochondrial function and metabolism
In many papers that focus on the condition of animals in natural environments, condition is defined as
the amount of body fatusually mass-corrected for
body size but sometimes actual amount of fat in the
body [discussed by Hill (2011)]. This conceptualization of condition is flawed for most animals in most
environments because it assumes that animals are
selected to maximize their amount of body fat, an
assumption that often is not true (Rogers 1987;
Witter and Cuthill 1993). However, there does
seem to be a fundamental connection between condition and metabolism. Not coincidentally, mitochondrial
dysfunction
and,
in
particular,
dysfunction of mitochondrial bioenergetics, has
taken center stage in biomedical research on metabolic disorders (Koene and Smeitink 2011), including
diabetes (Lane 2006), and in studies focused on diet
and aging (Keagy et al. 2011; Shutt and McBride
2013). Cellular respiration in mitochondria provides
the link between stress-response systems and metabolic regulation and function (Metallo and Vander

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Fig. 2 A conceptual framework for the connections between the

stress-response system, mitochondrial function, and key aspects
of individual performance. Stressors affect various aspects of
mitochondrial function via hormonal and non-hormonal signaling
molecules, especially glucocorticoids via the HPA axis. Changes in
mitochondrial function in turn affect a host of key aspects of
the performance of individuals, including ATP production, heat
production via uncoupling of the inner membrane, metabolic
rate, lipogenesis, immune responsiveness, and oxidative state.
Conventional views of the connections between ornamentation
and the stress axis have focused on the effects of hormones per
se, but moving the focus to the effects of mitochondria, under
regulation of hormones, holds promise of clarifying the links
between stress, condition, and ornamentation.

G. E. Hill

Cellular respiration and condition

Stress, condition, and ornamentation

I propose that the widely discussed associations between glucocorticoids, stress, ornamentation, and
immune responses (e.g., Buchanan 2000; Bortolotti
et al. 2009) arise as stressors affect mitochondrial
function and hence affect ornamentation and performance, with hormones mediating these responses
(Fig. 1). If this hypothesis is correct, then fundamental advances in understanding of responsiveness to
stress will come not through studies of the mediators
of metabolic responses but through studies of mitochondrial function.

Linking ornamentation to cellular

respiration
Behavioral displays
The simplest links between cellular respiration and
ornamentation involve ATP. If production of an ornament demands so much energy that high levels of
ATP are required, then necessarily there is a direct
connection between ornamentation and cellular respiration. Such a link between ornamentation and capacity for production of ATP is best demonstrated in
the classic work on sexual selection in Colias butterflies. These insects were studied under variable thermal conditions, and different allelic variants of
phosphoglucose isomerase (PGI) were favored in

different environments (Watt et al. 1983). PGI is

responsible for the second step of glycolysis and
thus plays a key role in production of ATP.
Whether or not males had the correct PGI type for
their thermal environment influenced their flight-display and females used flight-display as an important
criterion for choosing a mate (Watt et al. 1986).
Thus, the ornament (flight-display) served as an
honest signal of functionality of the glycolytic system
of a male under thermal stress, which has direct
consequences for fitness (Watt et al. 1983). In this
example it is efficiency of glycolysis rather than
OXPHOS that is signaled by the behavioral display,
but OXPHOS efficiency was not investigated.
OXHPOS efficiency would also affect output of
ATP and hence flight-display within this same
Colias system.
Note that in this Colias butterfly system, it is the
capacity to produce ATP rather than the size of the
pool of previously produced energy that is signaled
by flight displays. There is a need for in-time production of energy at a high rate for maximal flightdisplays. Thus, in the Colias example there is no need
to invoke tradeoffs between the use of energy for
body maintenance versus its use for ornamentation
(reviewed by Hill 2011). Indeed, there is little empirical support for tradeoffs in the use of stored energy
as the basis for honest signaling in any system, and
the shared-pathways hypothesis invokes no such tradeoffs. If the production of ornaments is dependent
on immediate production of ATP and ATPproduction is derived from the functionality of cellular respiration, then ornamental traits can serve as
direct windows into the functionality of cellular respiration. The sorts of links between capacity for
energy-production,
system-performance,
matechoice, and cellular respiration that were observed
for Colias butterflies seem likely to exist for many
energy-demanding behavioral displays in a wide
range of species.
Given that all functions of the body require
energy, there is potential for competing energy demands to restrict production of ornaments, as proposed by Rowe and Houle (1996). However, a
healthy system can respond to an increased
demand for energy by increasing output (Barja
2007; Lane 2011b). I propose that it is not the availability of energy per se that is likely to be signaled by
ornamentation but the capacity to produce energy.
I predict that many of the behavioral displays of
animals serve as uncheatable signals of the capacity for efficient energy production via cellular
respiration.

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Heiden 2013; Morava and Kozicz 2013; Scarpulla

2012).
One especially interesting link between environmental stress and the production of ATP and ROS
via OXPHOS is the metabolic intermediate nicotinamide adenine dinucleotide (NAD). NAD is a
central regulator of cellular energy homeostasis
(Karpac and Jasper 2013) and the maintenance of
an optimal NAD/NADH ratio is essential for a
fully functional electron-transport system and high
output of ATP associated with low production of
ROS. The synthesis and catabolism of NAD is sensitive to environmental conditions, especially nutrition and pathogens, thereby linking environmental
stressors to metabolic activity (Hootkooper et al.
2013; Houtkooper et al. 2010). At present, metabolic
studies of wild animals in ecological contexts are
limited to measures of body-composition, oxygen
consumption, and basal metabolic rates (Speakman
et al. 2003). New insights into the mechanistic links
between cellular respiration, fat stores, and ornamentation should emerge as studies begin to include
specific pathways related to the control of mitochondrial processes.

Carotenoid pigmentation

can signal respiratory efficiency, a recent study found

that the brightness of yellow coloration in American
Goldfinches (Cardeulis tristis) was significantly positively correlated with resting metabolic rate (Kelly
et al. 2012). Carotenoid signaling systems are prime
arenas for testing the hypothesis that ornamental
traits signal cellular respiration.
Other forms of pigmentation might also be linked
to mitochondrial function but the connections to
cellular respiration are not as clear as with carotenoids. Recent studies have shown that basic patterns
of light/dark coloration among species of animals, as
well as between color morphs within species, are
under control of melanocortin-1-receptor (MC1R)
(Mundy et al. 2004). Ducrest et al. (2008) highlighted the connections between proopiomelanocortins (POMC), which bind MC1R and which in turn
control the darkness of plumage and pelage, and a
host of cellular pathways including mitochondrial
pathways that are linked to POMC through melanocortin. The same POMC that binds MC1R also binds
melanocortin receptors, which in turn play roles in
the control of immune-function and regulation of
energy, and are linked to the HPA axis (Ducrest
et al. 2008). At this point, links between cellular respiration and individual variation in melanin pigmentation are indirect, and weak connections between
mitochondrial function and melanin systems may
be the reason that between-individual variation in
melanin ornamentation tends not to be as closely
linked to individual performance as is carotenoid
pigmentation (Hill and Brawner 1998; McGraw and
Hill 2000); but see Griffith et al. (2006).
Displays of cognitive and motor ability
Some ornamental traitssuch as the production of
multifarious songs, the rendering of intricate and
complicated dances, the creation of complex nests
and bowersare founded on cognitive ability. The
production and maintenance of the central nervous
system are among the most energy-demanding of all
system-processes (Wallace 2008; Vannuvel et al.
2013; Wang et al. 2013), so cognitive function
could simply relate to OXPHOS through a high
demand for ATP (Federico et al. 2012), as described
above. However, the links between mitochondrial
function and neurological function are far more
complex than simply the production of ATP
(Droge 2002; Lin and Beal 2006).
Associations between cellular respiration and neurological function have been studied primarily
within the realm of human neurological disorders.
Mitochondrial dysfunction has been linked to several

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Carotenoid coloration is among the classes of ornaments that are most frequently studied within the
context of condition-dependent signaling (Cotton
et al. 2006; Hill 2007; Garratt and Brooks 2012).
Carotenoids were first proposed to be honest signals
of the quality of a male because carotenoid pigments
were viewed as scarce resources that were difficult to
accrue such that only high-quality males could display bright coloration (Endler 1980; Hill 1992). More
recently, the focus has been on the resource-tradeoff
hypothesis, wherein carotenoids are proposed to be
essential, but limited, resources needed for immunedefense and protection against free radicals (Mller
et al. 2000; Alonso-Alvarez et al. 2007, 2009). By this
hypothesis, only high-condition males can sacrifice
carotenoid resources for ornamentation. However,
even when access to carotenoid resources is not limiting, individuals often display significant variation in
carotenoid coloration (Bortolotti et al. 1996; Karu
et al. 2008).
The hypothesis that ornamental coloration is a
signal of the functionality of cellular respiration
(Hill and Johnson 2012) presents a novel explanation
for the associations between carotenoid coloration
and measures of performance such as the production
of protein structures (Hill and Montgomerie 1994),
oxidative stress (Cote et al. 2010; Perez-Rodrguez
et al. 2010), immunocompetence (Blount et al.
2003; McGraw and Ardia 2003), body fat (PerezRodrguez and Vinuela 2008), and aerobic capacity
(Kelly et al. 2012; Mateos-Gonzalez et al. 2014). The
key assumption of this shared-pathway hypothesis as
it applies to carotenoids is that the mechanisms of
carotenoid pigmentation are closely tied to mitochondrial function (Hill and Johnson 2012, 2013;
Johnson and Hill 2013).
With few exceptions, animals attain carotenoidbased red coloration by oxidizing dietary yellow carotenoid pigments into ketolated products with a red
hue (Goodwin 1984; McGraw 2006). This process of
carotenoid ketolation is sensitive to oxidative conditions in cells and is thus inherently tied to OXPHOS
(Hill and Johnson 2012). Moreover, it has been proposed that ketolation of dietary carotenoids takes
place on the inner mitochondrial membrane in
close association with electron-transport complexes,
such that respiratory efficiency dictates the production of color (Johnson and Hill 2013). For displays
of non-ketolated carotenoids, different mechanisms
have been proposed to link the production of color
to mitochondrial function (Hill and Johnson 2012).
In support of the hypothesis that yellow xanthophylls

G. E. Hill

Cellular respiration and condition

Conclusions
Current theory proposes that stress, condition, and
ornamentation are linked through energy stores, with
condition reflecting the pool of available energy that
is needed for both ornamentation and body maintenance. This resource-tradeoff view of the associations
between stress, condition, and ornamentation, however, is not supported by many studies of either
model or non-model organisms in which resources
are provided ad libitum and stress-responsiveness
and ornamentation still vary among individuals.
Indeed, the resource-tradeoff hypothesis is a conceptual framework that is contradicted by every-day experiences. We provide our pets, our livestock, and
ourselves with unlimited access to energy, yet we
still observe substantial differences in all manner of
performances from running-endurance to disease resistance to longevity. I propose that stress, condition,
and ornamentation are connected not by energy

reserves, but through the capacity to efficiently produce energy, which is a product of the genotype,
epigenotype, and somatic state (Hill 2011; Fig. 1).
I further propose that condition-dependent ornamental traits evolved specifically as signals of cellular
respiration and the capacity to resist the disruptive
effects of stressors. Efficiency of cellular respiration is
the core aspect of a prospective mate about which a
choosing female should most desire information
(Hill and Johnson 2013), and ornamentation gives
females essential and otherwise imperceptible information about the cellular respiration of prospective
mates.

Acknowledgements
Wendy Hood, Haruka Wada, Amy Skibiel, and the
Hill/Hood/Wada laboratory groups provided valuable feedback on the manuscript.

Funding
IOS0923600. The symposium Stress, condition, and
ornamentation at the 2014 meeting at the Society of
Integrative and Comparative Biology was supported
by NSF grant DEB1359537 to W. R. Hood and
by SICB Divisions: Animal Behavior, Comparative
Endocrinology,
Ecology
&
Evolution,
and
Comparative Physiology & Biochemistry.

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