Staples 2013 Abstract MiP2013

From Bioblast
Staples JF(2013) Mechanisms of mitochondrial metabolic suppression in hibernation. Mitochondr Physiol Network 18.08.

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James Staples

MiP2013, Book of Abstracts Open Access

Staples JF (2013)

Event: MiPNet18.08_MiP2013

In winter mammalian hibernators, such as the 13-lined ground squirrel (Ictidomys tridecemlineatus), enter a state of torpor where metabolic rate is suppressed by ca. 90%, and body temperature (Tb) subsequently declines towards freezing. These changes are fully reversed during arousals, which occur spontaneously every 5-14 days throughout the winter. Arousals return animals to full euthermia for ca. 1 day before they enter another bout of torpor. This cycle is apparently driven by endogenous signals, and offers an excellent natural model to study plasticity of many physiological functions, including mechanisms of metabolic regulation.

The reversible suppression of whole-animal metabolism in hibernation is mirrored by some aspects of mitochondrial oxidative phosphorylation. In liver mitochondria isolated from torpid animals, OXPHOS capacity fueled by succinate oxidation is ca. 70% lower than in euthermic animals, even when measured at the same in vitro temperature (37 Β°C). Torpid suppression of mitochondrial respiration may conserve endogenous fuels and minimize damage by ROS, but it is not evident in all tissues, including cardiac muscle and forebrain. Moreover this suppression depends on several factors, including oxidative substrate and assay temperature. For example, in skeletal muscle mitochondria respiration is suppressed in torpor by ca. 35%, but only with succinate, and only when measured at 37 oC [1].

In liver mitochondria suppression of OXPHOS capacity occurs early during entrance into torpor, declining by 70% before Tb falls to 30 oC [2]. Conversely, reversal of suppression during arousal occurs only gradually; even after Tb rises from 5 oC to 30 oC, respiration is only 50% of values of fully aroused animals [3]. This β€œfast in, slow out” pattern suggests that temperature-sensitive mechanisms are responsible for the reversible suppression of mitochondrial metabolism.

In torpor, both intact mitochondria and succinate dehydrogenase (SDH) have higher apparent affinity for succinate, but SDH is inhibited by ca. 25%, probably by oxaloacetate (OAA) [1]. Reversal of OAA inhibition restores SDH activity, but does not fully β€œrescue” OXPHOS capacity to euthermic levels [3]. Recent phosphoproteomic analyses revealed seasonal (i.e. summer vs. winter) differences in the phosphorylation state of several mitochondrial proteins, but no differences between torpor and arousal. Future experiments will examine potential torpid inhibition of oxidative phosphorylation complexes by measuring their redox state in intact mitochondria using rapid-scanning optical spectrometry. We will also examine changes in mitochondrial protein acetylation state using immunoblot analysis.


β€’ O2k-Network Lab: CA London Staples JF


Labels: MiParea: Respiration, Comparative MiP;environmental MiP 


Organism: Other mammals  Tissue;cell: Liver  Preparation: Isolated mitochondria  Enzyme: Complex II;succinate dehydrogenase  Regulation: Inhibitor, Substrate, Temperature  Coupling state: OXPHOS  Pathway:HRR: Oxygraph-2k 

MiP2013 

Affiliations and author contributions

Dept of Biology, University of Western Ontario,Canada. - Email: [email protected]

References

  1. Brown JCL, Chung DJ, Cooper AN, Staples JF (2013) Regulation of succinate-fuelled mitochondrial respiration in liver and skeletal muscle of hibernating thirteen-lined ground squirrels. J Exp Biol 216: 1736-1743.
  2. Chung D, Lloyd GP, Thomar RH, Guglielmo CG, Staples JF (2011) Mitochondrial respiration and succinate dehydrogenase are suppressed early during entrance into a hibernation bout, but membrane remodeling is only transient. J Comp Physiol B 181: 699-711.
  3. Armstrong C, Staples JF (2010) The role of succinate dehydrogenase and oxaloacetate in mitochondrial metabolism during mammalian hibernation and arousal. J Comp Physiol B 180: 775-783.


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