Science 2011 Heldmaier 866 7 Commentary

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DOI: 10.1126/science.1203192, 866 (2011);331Science

Gerhard HeldmaierLife on Low Flame in Hibernation

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PERSPECTIVES

both the AM and the NF symbioses are based

on the shared activity of a set of plant genes,

SYMgenes (35). This indicates that bacte-

ria hijacked the signal transduction pathway

that fungi had used to gain entry into plant

tissues and cells. Op den Camp et al. provide

evidence that inParasponia, the only nonle-

gume partner of rhizobia, a single receptor

can recognize both the fungal and bacterial

signals and induce the common SYM path-

way to promote the intracellular accommoda-

tion of the partner microorganisms.

Op den Camp et al. used Rhizobium

strains, some of which were able to form

nodules, and some of which were unable to

form nodules, to prove that bothParasponia

and legumes use lipochito-oligosaccharides

called Nod factors to induce nodule develop-

ment. They also showed that Nod factors act

similarly in both symbioses via a common

signaling cascade; inParasponia, the intro-

duction of a dominant active form of calcium/

calmodulin-dependent kinase (CCaMK), akey element of this pathway, resulted in spon-

taneous nodulation, as in legumes.

Op den Camp et al. also provide insight

into how bacterial Nod factor receptors

(NFRs) evolved from receptors involved in

plant-fungi partnerships. The most-studied

legumes recognize rhizobiaor, more accu-

rately, the bacterial Nod factorsvia a pair

of LysM-type receptor-like kinases, NFR1/

LYK3 and NFR5/NFP (6, 7). Because these

NFRs are specif ic to bacterial symbiosis,

investigators had hypothesized that they

evolved either by duplication of the mycor-rhiza-specific receptors, which then gained

new functions, or by the recruitment of new

receptors that turned on the common signal-

ing pathway. Op den Camp et al.s analysis

indicates that receptor duplication was not

essential for plants to acquire the ability to

form a symbiotic relationship with NF bac-

teria. Instead, the presence of a single NFR5-

like receptor inParasponia,and its indispens-

able role in both symbioses, strongly suggests

that rhizobia entered symbiotic interactions

with plants through the same entrance used

by mycorrhizal fungi. It also means that the

molecular keycard that opens the door

to plant partnerships for both bacteria and

fungithe bacterial Nod factor and mycor-

rhizal (Myc) factormust be very similar.

Indeed, Maillet et al. (8) recently described

the Myc factors of AM fungi as lipochito-oli-

gosaccharide molecules that are very similar

to Nod factors.

These results raise several questions: Why

is the appearance of nitrogen-fixing nod-

ules, especially rhizobial ones, restricted to

a small fraction of mycorrhizal plants? Howdo plants discriminate between symbiotic

fungi and bacteria? Was it necessary for host

plants to distinguish between the microbes

to create different niches? Studies of genes

from related plants suggest that plant fami-

lies establishing rhizobial or actinorhizal

(Frankia) symbioses belong to the same large

lineage. This raises the possibility that, dur-

ing the evolution of flowering plants, a pre-

disposition for symbiotic nodule formation

originated only once (9). Did this predispo-

sition occur by changing the activity of one

or more component(s) of the common sym-biotic pathway, for example, by enabling it to

provide different outputs?

Both bacteria and mycorrhizal fu

induce changes in intracellular calci

(Ca2+-) concentrations (termed calcium s

ing). However, the frequency and dura

of the oscillations, as well as the speed of

movement, are different in the two sym

ses (10). Early elements of the common S

pathway, such as the LysM-type recep

and another receptor protein, the symbi

receptor kinase (SYMRK), are required

the induction of the calcium spiking, whic

then deciphered by CCaMK. It will be in

esting to compare calcium spiking upon

zobial and fungal inoculations in species

possess dual-functioning receptors.

There is not yet enough systematic d

from different plant lineages to determ

exactly how molecules like SYMRK

CCaMK contributed to the evolution o

predisposition to nodule formation. The

challenge is to find out why lineages w

predisposition for nodulation (for ex

ple, certain legumes) are unable to estabNF symbiosis.

References

1. R. Op den Campet al.,Science331, 909 (2011).

2. M. J. Harrison,Annu. Rev. Plant Physiol. Plant Mol. B

50, 361 (1999).

3. C. Kistneret al., Plant Cell17, 2217 (2005).

4. K. Markmannet al., PLoS Biol.6, e68 (2008).

5. C. Chen, M. Gao, J. Liu, H. Zhu,Plant Physiol.145,

(2007).

6. S. Radutoiuet al., Nature425, 585 (2003).

7. H. Kouchiet al., Plant Cell Physiol.51, 1381 (2010

8. F. Mailletet al., Nature469, 58 (2011).

9. D. E. Soltiset al., Proc. Natl. Acad. Sci. U.S.A.92, 2

(1995).

10. S. Kosutaet al., Proc. Natl. Acad. Sci. U.S.A.105, 98

(2008).

Life on Low Flame in Hibernation

PHYSIOLOGY

Gerhard Heldmaier

In hibernating black bears, changes in

metabolic rate and core body temperature

occur independently.

Do bears really hibernate? Their high

body temperature during winter dor-

mancy has raised some doubt aboutthis behavior, as it is unlike the pronounced

decreases observed in small mammals that

enter this nonactive state. On page 906 of

this issue, Tien et al. (1) show that bears do

indeed hibernate. Through continuous mea-

surement of oxygen consumption, body tem-

perature, and heart, muscle, and brain activ-

ities, the authors show that black bears dis-

play unusual patterns of metabolic and ther-

mal regulation during hibernation as well as

when they emerge from this resting state inthe spring.

Hibernation is a powerful behavior that

reduces energy costs in mammals. However,

in small mammals, it is frequently interrupted

by arousals (2, 3), thereby reducing its effec-

tiveness. Generally, after entrance into torpor,

deep torpor is maintained for 1 or 2 weeks

with body temperature close to the freezing

point of body fluids, and is terminated by

an arousal for about 1 day. During arousal,

body temperature rises to a normal 36C by

endogenous heat production. Collectiv

the arousal episodes require about 80%

the entire energy cost of the animal durthe hibernation season. The reasons for

repeated arousals are still a mystery, but t

may allow for the repair of neuronal dam

induced by prolonged hypometabolism

brain inactivity at low temperature (4, 5).

Spontaneous hibernation behavior is

ficult to observe in captive animals, so

study has mostly relied on field studie

subjects in their natural habitat, or on

mals kept in conditions similar to their

ural environment. Studying large mammAnimal Physiology, Philipps Universitaet, Marburg, Hessen35043, Germany. E-mail: [email protected]

10.1126/science.12

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CORRECTED 1 APRIL 2011; SEE LAST PAGE


3/4www.sciencemag.org SCIENCE VOL 331 18 FEBRUARY 2011

PERSPECTIV

(at least 10 kg) is particularly difficult

because of the challenges of continuous and

long-term monitoring. Tien et al. observed

five Alaskan black bears (Ursus americanus)

(two females and three males ranging in body

mass from 34.3 to 103.9 kg) that were kept in

outdoor enclosures in a forest near Fairbanks,Alaska. The bears hibernated in isolated

wooden nest boxes, which allowed continu-

ous observation and measurement of oxygen

consumption and body temperature as well as

monitoring of physiological activities from

implanted transmitters. The authors observed

that during the hibernation period (November

to March), the bears did not display repeated

arousals, but instead showed multiday oscil-

lations of body temperature between 30and

36C. Such a lack of periodic arousals dur-

ing hibernation has so far only been observed

in one small mammal [fat-tailed lemur (6)].

However, Tien et al. found that the hiber-nating bears reduced their metabolic rate to

75% below basal metabolic rate (BMR). The

observed minimum metabolic rate in hiber-

nating bears (0.056 ml O2g1hour1) is within

the range of those observed in small hibernat-

ing mammals (0.02 to 0.06 ml O2g1hour1)

(2, 3). This implies that bears use the entire

mammalian scope of metabolic inhibition in

torpor and are true hibernators. This reduction

of metabolic rate to 75% below BMR is sub-

stantially less prominent than that for small

mammals (98% below BMR). The difference

is largely due to the allometric scaling of BMR,

indicating that hibernation is more effective in

small mammals below 1 kg body mass.

Tien et al. also observed that when

the bears emerged from their dens in mid-

April, they had a normal body temperatureof 36.6C. Yet, they maintained a low meta-

bolic rate that was 47% below their BMR,

and it took several weeks for it to rise to that

of the active season (2.76 ml O2g1hour1). It

is generally assumed that BMR is a species-

specific constant that is necessary to maintain

the vital physiological functions of an endo-

thermic mammal resting at thermoneutrality.

The findings of Tien et al. show that bears

can maintain their vital functions with a met-

abolic rate that is reduced to nearly half of

that normally required in an active state, indi-

cating that BMR is not a constant but a physi-

ologically controlled variable.Transition into the torpid state includes

three processes. Thermoregulatory heat pro-

duction (by shivering or nonshivering thermo-

genesis) is inhibited because thermoregula-

tion is adjusted to a lower body temperature.

Metabolic rate is depressed below the BMR

at normothermic body temperature (active

metabolic inhibition). This inhibition can be

assisted by temperature effects on metabolic

rate. Tien et al. make the surprising finding

that in hibernating bears, metabolic depres-

sion is largely achieved by active metaboli

inhibition, whereas temperature effects pla

only a minor role. In small mammals tha

hibernate, active inhibition and temperature

related metabolic depression, on average, ma

each be responsible for about 50% of tot

metabolic depression (3, 7, 8).

The molecular mechanisms and biochem

cal pathways that underlie metabolic adjus

ment in torpor are still unclear. In genera

torpor metabolism involves inhibition of pro

cesses that generate adenosine 5-triphosphat

such as glycolysis (metabolism is rerouted t

lipid utilization instead) and mitochondri

respiration, as well as energy-consuming pro

cesses such as transcription, translation, an

protein degradation (911). This ultimatel

impairs cell proliferation and differentiation

However, entrance into torpor also require

increased expression of hibernation-specifi

genes to support lipid metabolism, gluconeo

genesis, cytoprotection, and other measure

required to maintain cells (12, 13).In most mammalian orders, one or sever

species use torpid metabolic depression. Th

greatest numbers are found among marsup

als, rodents, and bats, but also in small num

bers in insectivores, primates, and elephan

shrews; and it is likely that more such exam

ples will be discovered in large mammal

(14). Although long considered an adaptatio

to cold, hibernation is also found in tropic

animals and desert species, and, as in bear

can occur without substantial drops in bod

temperature. Perhaps we will find that

hypometabolic state is the primary means bwhich most, if not all mammals, can reduc

their energy expenditures for prolonged per

ods of time.

References 1. . Tienet al.,Science331, 906 (2011).

2. F. Geiser, T. Ruf,Physiol. Biochem. Zool.68, 935 (1995

3. G. Heldmaier, S. Ortmann, R. Elvert,Respir. Physiol. Ne

robiol.141, 317 (2004).

4. J. Ruedigeret al.,Synapse61, 343 (2007).

5. J. T. Stieleret al., PLoS ONE6, e14530 (2011).

6. K. H. Dausmann, J. Glos, G. Heldmaier,J. Comp. Physio

B179, 345 (2009).

7. C. L. Buck, B. M. Barnes,Am. J. Physiol.279, R255

(2000).

8. G. Heldmaier, R. Elvert, inLife in the Cold: Evolution,

Mechanisms, Adaptation and Application, B. M. Barnes

H. V. Carey, Eds. (Univ. of Alaska, Fairbanks, 2004), pp

185198.

9. F. van Breukelen, S. Martin,J. Comp. Physiol. B172, 35

(2002).

10. H. V. Carey, M. T. Andrews, S. L. Martin,Physiol. Rev.83

1153 (2003).

11. J. F. Staples, J. C. L. Brown,J. Comp. Physiol. B178, 81

(2008).

12. M. T. Andrews,Bioessays29, 431 (2007).

13. P. Morin Jr., K. B. Storey,Int. J. Dev. Biol.53, 433 (2009

14. W. Arnoldet al.,Am. J. Physiol.286, R174 (2004).

Barely active bear?Black bears emerging from hibernation have a metabolic rate that is nearly half of thatfound in a normal active state.

10.1126/science.12031CREDIT:COMSTOCK

Published by AAAS


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CORRECTIONS & CLARIFICATIONS

www.sciencemag.org SCIENCE ERRATUM POST DATE 1 APRIL 2011

ERRATUM

Perspectives:Life on low flame in hibernation by G. Heldmaier (18 February, p. 866). Inthe fourth paragraph, the basal metabolic rate of bears was incorrect. The correct figure is0.276 ml O

2g1hour1.

CORRECTIONS & CLARIFICATIONS

Post date 1 April 2011

Science 2011 Heldmaier 866 7 Commentary

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