Life on Low Flame in Hibernation Gerhard Heldmaier Science 331, 866 (2011); DOI: 10.1126/science.

1203192

This copy is for your personal, non-commercial use only.

Permission to republish or repurpose articles or portions of articles can be obtained by following the guidelines here. The following resources related to this article are available online at www.sciencemag.org (this information is current as of November 19, 2013 ): A correction has been published for this article at: http://www.sciencemag.org/content/332/6025/36.2.full.html Updated information and services, including high-resolution figures, can be found in the online version of this article at: http://www.sciencemag.org/content/331/6019/866.full.html A list of selected additional articles on the Science Web sites related to this article can be found at: http://www.sciencemag.org/content/331/6019/866.full.html#related This article cites 13 articles, 2 of which can be accessed free: http://www.sciencemag.org/content/331/6019/866.full.html#ref-list-1 This article has been cited by 1 articles hosted by HighWire Press; see: http://www.sciencemag.org/content/331/6019/866.full.html#related-urls This article appears in the following subject collections: Anatomy, Morphology, Biomechanics http://www.sciencemag.org/cgi/collection/anat_morp

Science (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. Copyright 2011 by the American Association for the Advancement of Science; all rights reserved. The title Science is a registered trademark of AAAS.

Downloaded from www.sciencemag.org on November 19, 2013

If you wish to distribute this article to others, you can order high-quality copies for your colleagues, clients, or customers by clicking here.

PERSPECTIVES

CORRECTED 1 APRIL 2011; SEE LAST PAGE

receptors that turned on the common signaling 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 bacteria. Instead, the presence of a single NFR5like receptor in Parasponia, and its indispensable 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 mycorrhizal (Myc) factormust be very similar. Indeed, Maillet et al. (8) recently described the Myc factors of AM fungi as lipochito-oligosaccharide molecules that are very similar to Nod factors. These results raise several questions: Why is the appearance of nitrogen-fixing nodules, especially rhizobial ones, restricted to a small fraction of mycorrhizal plants? How do 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 families establishing rhizobial or actinorhizal (Frankia) symbioses belong to the same large lineage. This raises the possibility that, during the evolution of owering plants, a predisposition for symbiotic nodule formation originated only once (9). Did this predisposition occur by changing the activity of one or more component(s) of the common symbiotic pathway, for example, by enabling it to provide different outputs? Both bacteria and mycorrhizal fungi induce changes in intracellular calcium (Ca2+-) concentrations (termed calcium spiking). However, the frequency and duration of the oscillations, as well as the speed of Ca movement, are different in the two symbioses (10). Early elements of the common SYM pathway, such as the LysM-type receptors and another receptor protein, the symbiosis receptor kinase (SYMRK), are required for the induction of the calcium spiking, which is then deciphered by CCaMK. It will be interesting to compare calcium spiking upon rhizobial and fungal inoculations in species that possess dual-functioning receptors. There is not yet enough systematic data from different plant lineages to determine exactly how molecules like SYMRK and CCaMK contributed to the evolution of a predisposition to nodule formation. The real challenge is to nd out why lineages with predisposition for nodulation (for example, certain legumes) are unable to establish NF symbiosis.
1. R. Op den Camp et al., Science 331, 909 (2011). 2. M. J. Harrison, Annu. Rev. Plant Physiol. Plant Mol. Biol. 50, 361 (1999). 3. C. Kistner et al., Plant Cell 17, 2217 (2005). 4. K. Markmann et al., PLoS Biol. 6, e68 (2008). 5. C. Chen, M. Gao, J. Liu, H. Zhu, Plant Physiol. 145, 1619 (2007). 6. S. Radutoiu et al., Nature 425, 585 (2003). 7. H. Kouchi et al., Plant Cell Physiol. 51, 1381 (2010). 8. F. Maillet et al., Nature 469, 58 (2011). 9. D. E. Soltis et al., Proc. Natl. Acad. Sci. U.S.A. 92, 2647 (1995). 10. S. Kosuta et al., Proc. Natl. Acad. Sci. U.S.A. 105, 9823 (2008). 10.1126/science.1202342

both the AM and the NF symbioses are based on the shared activity of a set of plant genes, SYM genes (35). This indicates that bacteria 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 in Parasponia, the only nonlegume partner of rhizobia, a single receptor can recognize both the fungal and bacterial signals and induce the common SYM pathway to promote the intracellular accommodation 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 both Parasponia and legumes use lipochito-oligosaccharides called Nod factors to induce nodule development. They also showed that Nod factors act similarly in both symbioses via a common signaling cascade; in Parasponia, the introduction of a dominant active form of calcium/ calmodulin-dependent kinase (CCaMK), a key element of this pathway, resulted in spontaneous 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 accurately, the bacterial Nod factorsvia a pair of LysM-type receptor-like kinases, NFR1/ LYK3 and NFR5/NFP (6, 7). Because these NFRs are specific to bacterial symbiosis, investigators had hypothesized that they evolved either by duplication of the mycorrhiza-specic receptors, which then gained new functions, or by the recruitment of new

References

PHYSIOLOGY

Life on Low Flame in Hibernation

Gerhard Heldmaier

In hibernating black bears, changes in metabolic rate and core body temperature occur independently.

o bears really hibernate? Their high body temperature during winter dormancy has raised some doubt about this 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 measurement of oxygen consumption, body temperature, and heart, muscle, and brain activities, the authors show that black bears disAnimal Physiology, Philipps Universitaet, Marburg, Hessen 35043, Germany. E-mail: heldmaier@staff.uni-marburg.de

play unusual patterns of metabolic and thermal regulation during hibernation as well as when they emerge from this resting state in the 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 effectiveness. 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. Collectively, the arousal episodes require about 80% of the entire energy cost of the animal during the hibernation season. The reasons for the repeated arousals are still a mystery, but they may allow for the repair of neuronal damage induced by prolonged hypometabolism and brain inactivity at low temperature (4, 5). Spontaneous hibernation behavior is difficult to observe in captive animals, so its study has mostly relied on eld studies of subjects in their natural habitat, or on animals kept in conditions similar to their natural environment. Studying large mammals

866

18 FEBRUARY 2011 VOL 331 SCIENCE www.sciencemag.org

Published by AAAS

PERSPECTIVES
sion is largely achieved by active metabolic inhibition, whereas temperature effects play only a minor role. In small mammals that hibernate, active inhibition and temperaturerelated metabolic depression, on average, may each be responsible for about 50% of total metabolic depression (3, 7, 8). The molecular mechanisms and biochemical pathways that underlie metabolic adjustment in torpor are still unclear. In general, torpor metabolism involves inhibition of processes that generate adenosine 5-triphosphate such as glycolysis (metabolism is rerouted to lipid utilization instead) and mitochondrial respiration, as well as energy-consuming processes such as transcription, translation, and protein degradation (911). This ultimately impairs cell proliferation and differentiation. However, entrance into torpor also requires increased expression of hibernation-specic genes to support lipid metabolism, gluconeogenesis, cytoprotection, and other measures required to maintain cells (12, 13). In most mammalian orders, one or several species use torpid metabolic depression. The greatest numbers are found among marsupials, rodents, and bats, but also in small numbers in insectivores, primates, and elephant shrews; and it is likely that more such examples will be discovered in large mammals (14). Although long considered an adaptation to cold, hibernation is also found in tropical animals and desert species, and, as in bears, can occur without substantial drops in body temperature. Perhaps we will find that a hypometabolic state is the primary means by which most, if not all mammals, can reduce their energy expenditures for prolonged periods of time.
1. . Tien et al., Science 331, 906 (2011). 2. F. Geiser, T. Ruf, Physiol. Biochem. Zool. 68, 935 (1995). 3. G. Heldmaier, S. Ortmann, R. Elvert, Respir. Physiol. Neurobiol. 141, 317 (2004). 4. J. Ruediger et al., Synapse 61, 343 (2007). 5. J. T. Stieler et al., PLoS ONE 6, e14530 (2011). 6. K. H. Dausmann, J. Glos, G. Heldmaier, J. Comp. Physiol. B 179, 345 (2009). 7. C. L. Buck, B. M. Barnes, Am. J. Physiol. 279, R255 (2000). 8. G. Heldmaier, R. Elvert, in Life 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. B 172, 355 (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. B 178, 811 (2008). 12. M. T. Andrews, Bioessays 29, 431 (2007). 13. P. Morin Jr., K. B. Storey, Int. J. Dev. Biol. 53, 433 (2009). 14. W. Arnold et al., Am. J. Physiol. 286, R174 (2004). 10.1126/science.1203192

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

(at least 10 kg) is particularly difficult because of the challenges of continuous and long-term monitoring. Tien et al. observed ve 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 continuous 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 oscillations of body temperature between 30 and 36C. Such a lack of periodic arousals during hibernation has so far only been observed in one small mammal [fat-tailed lemur (6)]. However, Tien et al. found that the hibernating bears reduced their metabolic rate to 75% below basal metabolic rate (BMR). The observed minimum metabolic rate in hibernating bears (0.056 ml O2 g1 hour1) is within the range of those observed in small hibernating mammals (0.02 to 0.06 ml O2 g1 hour1) (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 substantially 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 midApril, they had a normal body temperature of 36.6C. Yet, they maintained a low metabolic 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 O2 g1 hour1). It is generally assumed that BMR is a speciesspecic constant that is necessary to maintain the vital physiological functions of an endothermic mammal resting at thermoneutrality. The ndings of Tien et al. show that bears can maintain their vital functions with a metabolic rate that is reduced to nearly half of that normally required in an active state, indicating that BMR is not a constant but a physiologically controlled variable. Transition into the torpid state includes three processes. Thermoregulatory heat production (by shivering or nonshivering thermogenesis) is inhibited because thermoregulation 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 nding that in hibernating bears, metabolic depres-

References

CREDIT: COMSTOCK

www.sciencemag.org SCIENCE VOL 331 18 FEBRUARY 2011

Published by AAAS

867

CORREcTIONS & CLARIFIcATIONS

eRRATUM

Post date 1 April 2011

Perspectives: Life on low flame in hibernation by G. Heldmaier (18 February, p. 866). In the fourth paragraph, the basal metabolic rate of bears was incorrect. The correct figure is 0.276 ml O2g1 hour1.

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