Rees, Bernard

English

University of New Orleans

University of New Orleans ScholarWorks@UNO Biological Sciences Faculty Publications Department of Biological Sciences 10-2002 Molecular Mechanisms of Metabolic Arrest: Life in Limbo (Book Review) Bernard Rees University of New Orleans, brees@uno.edu Follow this and additional works at: https://scholarworks.uno.edu/biosciences_facpubs  Part of the Biology Commons Recommended Citation Rees, B.B. 2002. Molecular mechanisms of metabolic arrest: life in limbo (book review). Journal of Experimental Biology 205: 2922-2956. This Book Review is brought to you for free and open access by the Department of Biological Sciences at ScholarWorks@UNO. It has been accepted for inclusion in Biological Sciences Faculty Publications by an authorized administrator of ScholarWorks@UNO. For more information, please contact scholarworks@uno.edu. Book Review 2955Life in limboMolecular mechanisms of metabolic arrest:life in limbo Edited by K. B. Storey SEB Seminar Series. Oxford, UK: BIOS Scientific Publishers Ltd.(2001)216 pp. ISBN 1 85996 2122£75.A wide variety of organismspossess the capacity toreversibly reduce metab-olism, either in responseto adverse environmentalconditions or as aprogrammed part of theirlife cycle. A hallmarkfeature of metabolic arrest inthese organisms is that thereis little or no decrease in thestructural or functionalintegrity of cells and tissues.The mechanisms used bythese organisms to decreasemetabolic rates and tosurvive at these lower rates is a fascinating biological question.The book Molecular mechanisms of metabolic arrest: life inlimbo, edited by K. B. Storey, attempts to tackle this question.The book begins with several chapters that examinemetabolic rate reduction during seasonal dormancy:hibernation in mammals; over-wintering in frogs and turtles;and summer dormancy (or estivation) in toads and snails. In thelead-off chapter, Storey reviews enzymatic correlates ofmetabolic depression during hibernation in ground squirrelsand during estivation in the spadefoot toad. The activities ofkey metabolic enzymes are modulated by multiple regulatorymechanisms, including both post-translational modification(e.g. phosphorylation) and transcriptional control. In theirchapter on mammalian hibernation, McCarron, Sieckmann, Yu,Frerichs, and Hallenbeck summarize evidence for plasma borneÔhibernation factorsÕ and describe changes occurring in braintissue that improve the tolerance of this tissue to low oxygen,low blood glucose, and low temperatures. This chapter alsoreviews a small number of genes whose expression changesduring hibernation, focussing on an increase in the expressionof the melatonin receptor measured in a variety of tissues.Perhaps, the authors contend, an increased sensitivity tomelatonin is linked to either the induction or maintenance ofhibernation. Both of these chapters cite identified genes whoselevels are altered during hibernation or estivation. For some ofthese, the link between gene expression and metabolicreorganization during dormancy has been established; forothers, this relationship has yet to be elucidated. An excellent chapter by Brand, Boutilier, Wass, St-Pierre,and Bishop evaluates the contribution of mitochondrial protonleakage to the metabolism of dormant animals. Over the pastdecade, Brand and his colleagues have found that as much as20Ð25% of the standard metabolic rate of a variety of animalscan be accounted for by the futile cycling of proton pumpingand leakage across the inner mitochondrial membrane. If theabsolute energy expenditure due to proton cycling were toremain constant during dormancy, then this process couldpotentially account for all of the metabolic rate of animalswhose metabolism is reduced by 80% or more. Concurrently,the efficiency of mitochondrial oxidative phosphorylationwould approach zero, a situation that would seem to defeat thepurpose of metabolic dormancy, i.e. preservation of energyreserves. Alternatively, this energetically costly process may becurtailed during dormancy, due to a lower proton conductanceof the inner mitochondrial membrane, lower maximum rates ofsubstrate oxidation, or a combination of both. Brand et al.examine these questions in over-wintering frogs and estivatingsnails. The rates of proton cycling in frog and snail tissues dropduring metabolic dormancy, and experiments with isolatedmitochondria suggest that the lower cycling is a result of lowerrates of substrate oxidation rather than changes in protonconductance. These results are intriguing and provide insightinto the general processes involved in metabolic suppressionduring dormancy.Another remarkable example of metabolic suppressionoccurs in certain species of freshwater turtles during long-termwinter submergence. Jackson addresses the contributions oflow temperature and low oxygen to the profound reduction ofmetabolic rate during dormancy. This chapter also includes abrief consideration of aquatic respiration by turtles. In additionto a dramatic reduction in metabolism, these animals displayan impressive tolerance of anoxia. Because the ÒtypicalÓvertebrate nervous system is exquisitely sensitive to hypoxicinjury, much attention has focused on the specializations ofturtle neurons that confer such marked anoxia tolerance. In theircontribution, Bickler, Donohoe, and Buck describe a decreasein the excitability and an increase in membrane resistance ofturtle neurons under anoxia. Both processes serve to limit ionfluxes during anoxia, thereby reducing the energetic costs ofion homeostasis and prolonging cell survival. Bickler andcolleagues present evidence that ion channel inactivationdepends upon a modest elevation in intracellular Ca2+ duringanoxia. These observations have led to the idea that specificlevels of Ca2+ are associated with dramatically differentconsequences: large elevations of Ca2+, as a result ofuncontrollable calcium influx typical of anoxia-sensitiveneurons, are ultimately toxic; small elevations of intracellularCa2+, as seen in turtle neurons, may be necessary to promotefull protection and neuronal survival. This concept of ÔCa2+windowsÕ may prove to be a fundamental insight into the abilityof certain tissues to survive anoxia. A chapter by Ashcroft andTrapp on ATP-sensitive potassium channels also addresses ionhomeostasis during metabolic transitions. This chapter presents2956 Book Reviewa detailed description of the structure and function of thechannel from mammalian tissues. The mechanistic linkbetween changes in metabolism and channel activity, however,remains elusive.There are two chapters on how low oxygen affectsthermostasis in organisms, i.e. the selection and maintenanceof body temperature. Wood explores the ability of animals tolower body temperature, either through physiological orbehavioral means, as a mechanism of metabolic rate reduction.Regulated hypothermia during hypoxia is widespread amonganimals, occurring in a variety of ectothermic and endothermicvertebrates, and several molecules have been examined aspotential signaling agents for this response. In addition to adecrease in oxygen demand at lower temperatures, otheradvantages that may accrue from a lower body temperature arean increase in hemoglobinÕs ability to bind oxygen at therespiratory surfaces and a decrease in the hypoxic ventilatoryresponse. Malvin extends the consideration of behavioralhypothermia as a strategy to cope with hypoxia to the protozoanParamecium caudatum. In a thermal gradient, this unicellularorganism selects a ÔpreferredÕ temperature and the temperatureselected varies with environmental oxygen: lower temperaturesare selected at lower oxygen tensions. This response has amarked effect on survival time during hypoxia. The widespreadnature of regulated hypothermia, coupled with the dramaticsurvival benefits, should stimulate further inquiry into themolecular events responsible for this process.There are also a pair of chapters on diapause, anendogenously programmed, metabolically dormant period thatoccurs at specific stages in the life cycle of several animals.Denlinger reviews diapause in insects and MacRae examinesdiapause in the brine shrimp Artemia franciscana. While indiapause, these organisms display incredible resistance to harshenvironments (e.g. extreme temperatures, desiccation, anoxia).Surveys of gene expression have identified a handful of mRNAtranscripts and protein products that are upregulated duringdiapause. These include the heat shock genes hsp23 and hsp70in insects and p26 in Artemia. These stress proteins presumablyhelp prevent protein denaturation or stabilize partiallydenatured proteins during diapause. In certain insects, theproliferating cell nuclear antigen is up-regulated immediatelyfollowing the termination of diapause, leading to the suggestionthat this gene may be involved in resumption of cell divisionafter diapause. In several insect examples, as well as inArtemia, whether an individual enters diapause is determinedby the environmental conditions experienced by the mother.The molecular bases of these maternal effects is an exciting andfertile area for future research.Rounding out the book are chapters on metabolicdormancy in yeast and plants. As described by Ruis, themolecular details of switching between various metabolicstates in response to environmental changes are probably bestdescribed in the budding yeast, Saccharomyces cerevisiae. Awide array of stresses will induce a generalized stressresponse, mediated, in part, by the binding of transcriptionfactors to stress-responsive elements in various genes. Proteinkinase A (PKA) plays a pivotal role in determining thesensitivity of yeast to stress by negatively regulating thesetranscription factors. Interestingly, PKA also regulates cellgrowth and division, filamentous invasion, meiosis andsporulation, thereby coupling the stress response to changesin growth and reproductive mode. This fascinating chapterdemonstrates the utility of a genetically tractable organismand illustrates the complexity of the molecular circuitryinvolved in changes in metabolic status of this organism. Thefinal chapter by Bartels examines desiccation-induceddormancy in resurrection plants, a small and diverse group ofplants that can withstand near complete dehydration (removalof >95% of tissue water). Measures of gene expression indehydrated tissues have revealed a broad spectrum of geneswhose expressions are altered relative to hydrated controls.Some of these confer desiccation resistance by stabilizingmembranes and proteins, whereas others are involved incarbohydrate metabolism, water balance, signal transduction,and gene regulation.The territory covered by this book is vast, due, in part, tothe fact that metabolic dormancy is a widespread biologicalphenomenon. Furthermore, it is apparent from these pagesthat the bases of metabolic arrest are diverse, and range fromchanges in gene expression to behavioral temperatureselection. A chapter summarizing this diversity would havebeen nice. The omission of such a chapter represents a missedopportunity to identify processes that unify the manyexamples of metabolic depression covered in this book.Although the scope of the book is a bit unwieldy, theindividual chapters are engaging, enlightening, and point thedirection for future research. It is clear that substantialprogress has been made in understanding the mechanisms ofmetabolic arrest, but to quote closing words of the firstchapter, Ômuch more remains to be learned about how natureturns down the fires of lifeÕ.Bernard B. ReesDepartment of Biological Sciences, University of New Orleans, NewOrleans, LA 70148, USAThe Journal of Experimental Biology 205, 2955-2956 (2002) © The Company of Biologists Ltd

Molecular Mechanisms of Metabolic Arrest: Life in Limbo (Book Review)

ScholarWorks @ The University of New Orleans

University of New Orleans 
ScholarWorks@UNO 
Biological Sciences Faculty Publications Department of Biological Sciences 
10-2002 
Molecular Mechanisms of Metabolic Arrest: Life in Limbo (Book 
Review) 
Bernard Rees 
University of New Orleans, brees@uno.edu 
Follow this and additional works at: https://scholarworks.uno.edu/biosciences_facpubs 
 Part of the Biology Commons 
Recommended Citation 
Rees, B.B. 2002. Molecular mechanisms of metabolic arrest: life in limbo (book review). Journal of 
Experimental Biology 205: 2922-2956. 
This Book Review is brought to you for free and open access by the Department of Biological Sciences at 
ScholarWorks@UNO. It has been accepted for inclusion in Biological Sciences Faculty Publications by an 
authorized administrator of ScholarWorks@UNO. For more information, please contact scholarworks@uno.edu. 
Book Review 2955
Life in limbo
Molecular mechanisms of metabolic arrest:
life in limbo 
Edited by K. B. Storey 
SEB Seminar Series. Oxford, UK: BIOS Scientific Publishers Ltd.
(2001)
216 pp. ISBN 1 85996 2122
£75.
A wide variety of organisms
possess the capacity to
reversibly reduce metab-
olism, either in response
to adverse environmental
conditions or as a
programmed part of their
life cycle. A hallmark
feature of metabolic arrest in
these organisms is that there
is little or no decrease in the
structural or functional
integrity of cells and tissues.
The mechanisms used by
these organisms to decrease
metabolic rates and to
survive at these lower rates is a fascinating biological question.
The book Molecular mechanisms of metabolic arrest: life in
limbo, edited by K. B. Storey, attempts to tackle this question.
The book begins with several chapters that examine
metabolic rate reduction during seasonal dormancy:
hibernation in mammals; over-wintering in frogs and turtles;
and summer dormancy (or estivation) in toads and snails. In the
lead-off chapter, Storey reviews enzymatic correlates of
metabolic depression during hibernation in ground squirrels
and during estivation in the spadefoot toad. The activities of
key metabolic enzymes are modulated by multiple regulatory
mechanisms, including both post-translational modification
(e.g. phosphorylation) and transcriptional control. In their
chapter on mammalian hibernation, McCarron, Sieckmann, Yu,
Frerichs, and Hallenbeck summarize evidence for plasma borne
Ôhibernation factorsÕ and describe changes occurring in brain
tissue that improve the tolerance of this tissue to low oxygen,
low blood glucose, and low temperatures. This chapter also
reviews a small number of genes whose expression changes
during hibernation, focussing on an increase in the expression
of the melatonin receptor measured in a variety of tissues.
Perhaps, the authors contend, an increased sensitivity to
melatonin is linked to either the induction or maintenance of
hibernation. Both of these chapters cite identified genes whose
levels are altered during hibernation or estivation. For some of
these, the link between gene expression and metabolic
reorganization during dormancy has been established; for
others, this relationship has yet to be elucidated. 
An excellent chapter by Brand, Boutilier, Wass, St-Pierre,
and Bishop evaluates the contribution of mitochondrial proton
leakage to the metabolism of dormant animals. Over the past
decade, Brand and his colleagues have found that as much as
20Ð25% of the standard metabolic rate of a variety of animals
can be accounted for by the futile cycling of proton pumping
and leakage across the inner mitochondrial membrane. If the
absolute energy expenditure due to proton cycling were to
remain constant during dormancy, then this process could
potentially account for all of the metabolic rate of animals
whose metabolism is reduced by 80% or more. Concurrently,
the efficiency of mitochondrial oxidative phosphorylation
would approach zero, a situation that would seem to defeat the
purpose of metabolic dormancy, i.e. preservation of energy
reserves. Alternatively, this energetically costly process may be
curtailed during dormancy, due to a lower proton conductance
of the inner mitochondrial membrane, lower maximum rates of
substrate oxidation, or a combination of both. Brand et al.
examine these questions in over-wintering frogs and estivating
snails. The rates of proton cycling in frog and snail tissues drop
during metabolic dormancy, and experiments with isolated
mitochondria suggest that the lower cycling is a result of lower
rates of substrate oxidation rather than changes in proton
conductance. These results are intriguing and provide insight
into the general processes involved in metabolic suppression
during dormancy.
Another remarkable example of metabolic suppression
occurs in certain species of freshwater turtles during long-term
winter submergence. Jackson addresses the contributions of
low temperature and low oxygen to the profound reduction of
metabolic rate during dormancy. This chapter also includes a
brief consideration of aquatic respiration by turtles. In addition
to a dramatic reduction in metabolism, these animals display
an impressive tolerance of anoxia. Because the ÒtypicalÓ
vertebrate nervous system is exquisitely sensitive to hypoxic
injury, much attention has focused on the specializations of
turtle neurons that confer such marked anoxia tolerance. In their
contribution, Bickler, Donohoe, and Buck describe a decrease
in the excitability and an increase in membrane resistance of
turtle neurons under anoxia. Both processes serve to limit ion
fluxes during anoxia, thereby reducing the energetic costs of
ion homeostasis and prolonging cell survival. Bickler and
colleagues present evidence that ion channel inactivation
depends upon a modest elevation in intracellular Ca2+ during
anoxia. These observations have led to the idea that specific
levels of Ca2+ are associated with dramatically different
consequences: large elevations of Ca2+, as a result of
uncontrollable calcium influx typical of anoxia-sensitive
neurons, are ultimately toxic; small elevations of intracellular
Ca2+, as seen in turtle neurons, may be necessary to promote
full protection and neuronal survival. This concept of ÔCa2+
windowsÕ may prove to be a fundamental insight into the ability
of certain tissues to survive anoxia. A chapter by Ashcroft and
Trapp on ATP-sensitive potassium channels also addresses ion
homeostasis during metabolic transitions. This chapter presents
2956 Book Review
a detailed description of the structure and function of the
channel from mammalian tissues. The mechanistic link
between changes in metabolism and channel activity, however,
remains elusive.
There are two chapters on how low oxygen affects
thermostasis in organisms, i.e. the selection and maintenance
of body temperature. Wood explores the ability of animals to
lower body temperature, either through physiological or
behavioral means, as a mechanism of metabolic rate reduction.
Regulated hypothermia during hypoxia is widespread among
animals, occurring in a variety of ectothermic and endothermic
vertebrates, and several molecules have been examined as
potential signaling agents for this response. In addition to a
decrease in oxygen demand at lower temperatures, other
advantages that may accrue from a lower body temperature are
an increase in hemoglobinÕs ability to bind oxygen at the
respiratory surfaces and a decrease in the hypoxic ventilatory
response. Malvin extends the consideration of behavioral
hypothermia as a strategy to cope with hypoxia to the protozoan
Paramecium caudatum. In a thermal gradient, this unicellular
organism selects a ÔpreferredÕ temperature and the temperature
selected varies with environmental oxygen: lower temperatures
are selected at lower oxygen tensions. This response has a
marked effect on survival time during hypoxia. The widespread
nature of regulated hypothermia, coupled with the dramatic
survival benefits, should stimulate further inquiry into the
molecular events responsible for this process.
There are also a pair of chapters on diapause, an
endogenously programmed, metabolically dormant period that
occurs at specific stages in the life cycle of several animals.
Denlinger reviews diapause in insects and MacRae examines
diapause in the brine shrimp Artemia franciscana. While in
diapause, these organisms display incredible resistance to harsh
environments (e.g. extreme temperatures, desiccation, anoxia).
Surveys of gene expression have identified a handful of mRNA
transcripts and protein products that are upregulated during
diapause. These include the heat shock genes hsp23 and hsp70
in insects and p26 in Artemia. These stress proteins presumably
help prevent protein denaturation or stabilize partially
denatured proteins during diapause. In certain insects, the
proliferating cell nuclear antigen is up-regulated immediately
following the termination of diapause, leading to the suggestion
that this gene may be involved in resumption of cell division
after diapause. In several insect examples, as well as in
Artemia, whether an individual enters diapause is determined
by the environmental conditions experienced by the mother.
The molecular bases of these maternal effects is an exciting and
fertile area for future research.
Rounding out the book are chapters on metabolic
dormancy in yeast and plants. As described by Ruis, the
molecular details of switching between various metabolic
states in response to environmental changes are probably best
described in the budding yeast, Saccharomyces cerevisiae. A
wide array of stresses will induce a generalized stress
response, mediated, in part, by the binding of transcription
factors to stress-responsive elements in various genes. Protein
kinase A (PKA) plays a pivotal role in determining the
sensitivity of yeast to stress by negatively regulating these
transcription factors. Interestingly, PKA also regulates cell
growth and division, filamentous invasion, meiosis and
sporulation, thereby coupling the stress response to changes
in growth and reproductive mode. This fascinating chapter
demonstrates the utility of a genetically tractable organism
and illustrates the complexity of the molecular circuitry
involved in changes in metabolic status of this organism. The
final chapter by Bartels examines desiccation-induced
dormancy in resurrection plants, a small and diverse group of
plants that can withstand near complete dehydration (removal
of >95% of tissue water). Measures of gene expression in
dehydrated tissues have revealed a broad spectrum of genes
whose expressions are altered relative to hydrated controls.
Some of these confer desiccation resistance by stabilizing
membranes and proteins, whereas others are involved in
carbohydrate metabolism, water balance, signal transduction,
and gene regulation.
The territory covered by this book is vast, due, in part, to
the fact that metabolic dormancy is a widespread biological
phenomenon. Furthermore, it is apparent from these pages
that the bases of metabolic arrest are diverse, and range from
changes in gene expression to behavioral temperature
selection. A chapter summarizing this diversity would have
been nice. The omission of such a chapter represents a missed
opportunity to identify processes that unify the many
examples of metabolic depression covered in this book.
Although the scope of the book is a bit unwieldy, the
individual chapters are engaging, enlightening, and point the
direction for future research. It is clear that substantial
progress has been made in understanding the mechanisms of
metabolic arrest, but to quote closing words of the first
chapter, Ômuch more remains to be learned about how nature
turns down the fires of lifeÕ.
Bernard B. Rees
Department of Biological Sciences, University of New Orleans, New
Orleans, LA 70148, USA
The Journal of Experimental Biology 205, 2955-2956 (2002) © The Company of Biologists Ltd


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Molecular Mechanisms of Metabolic Arrest: Life in Limbo (Book Review)

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