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Vertebrate cell death in energy-limited conditions and how to avoid it: what we might learn from mammalian hibernators and other stress-tolerant vertebrates

  • Unusual Model Systems for Cell Death Research
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Abstract

Dormancy in vertebrates may expose cells to acidosis, hypoxia/anoxia, oxidative damage, and extremes in temperature. All of these insults are known to be pro-apoptotic in typical vertebrate cells, especially mammals. Since dormancy is presumably the result of a need for energy conservation, the inherent energetic demand of replenishing cells that underwent apoptosis seems at odds with this strategy. This review will discuss processes to mitigate apoptosis and how these processes might be regulated in stress-tolerant vertebrates such as mammalian hibernators. As data directly addressing such issues are scarce and often conflicting, an apparently complex regulation of apoptosis seems to be at work. For example, apoptosis is mitigated during dormancy, key signaling events including the activation of caspase-3 may still occur. However, both passive, temperature-induced depression of apoptotic signaling as well as active suppression of apoptosis appear to work in synergy in these systems. In many instances cell death is prevented by simply avoiding the cellular triggers (e.g. leakage of proteins from the mitochondria or increases in intracellular calcium) that initiate apoptotic signaling. In this review we discuss what is known about programmed cell death in these under-studied models and highlight features of their physiology that likely support survival in the face of conditions that would induce cell death in typical vertebrate cells.

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Acknowledgments

All authors contributed equally to this work. The authors wish to thank the respective members of their laboratories for insight and suggestions. GK was supported by a grant from the Austrian Science Fund (FWF; Y212-B13 START). JEP was supported by grants from the National Science Foundation (IOB 0344578) and the American Heart Association (0335286N). FvB was supported by grants from the National Science Foundation (IOB 0448396) and the National Institutes of Health 2 P20 RR016464 from the INBRE Program of the National Center for Research Resources.

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Authors and Affiliations

  1. School of Life Sciences, University of Nevada, Las Vegas, NV, 89154, USA

    Frank van Breukelen

  2. Division of Developmental Immunology, Biocenter, Innsbruck Medical University, Innsbruck, Austria

    Gerhard Krumschnabel

  3. Department of Biology, Portland State University, Portland, OR, 97201, USA

    Jason E. Podrabsky

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  1. Frank van Breukelen
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  2. Gerhard Krumschnabel
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  3. Jason E. Podrabsky
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Correspondence to Frank van Breukelen.

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van Breukelen, F., Krumschnabel, G. & Podrabsky, J.E. Vertebrate cell death in energy-limited conditions and how to avoid it: what we might learn from mammalian hibernators and other stress-tolerant vertebrates. Apoptosis 15, 386–399 (2010). https://doi.org/10.1007/s10495-010-0467-y

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