bims-resufa Biomed News
on Respiratory supercomplex factors
Issue of 2019‒10‒27
two papers selected by
Vera Strogolova
Strong Microbials, Inc

  1. J Alzheimers Dis. 2019 Oct 14.
    Pepperberg DR.
      Cerebral hypoperfusion-induced hypoxia, a condition that impairs oxygen utilization and thus ATP production by mitochondrial oxidative phosphorylation (oxphos), is thought to contribute to neural degeneration in Alzheimer's disease. However, hypoxia upregulates the generation of amyloid-β (Aβ), a group of peptides known to impair/inhibit the electron transport chain (ETC) of reactions that support oxphos in the inner mitochondrial membrane (IMM). This is a hypothesis paper that reconciles the hypoxia-induced upregulation of Aβ with Aβ's ETC-inhibiting action and, specifically, posits an oxphos-enhancing effect of this inhibition under conditions of newly developing or otherwise mild hypoxia. This effect is typically transient; that is, under conditions of prolonged or severe hypoxia, the oxphos-enhancing activity is overwhelmed by Aβ's well-known toxic actions on mitochondria and other cellular components. The hypothesis is motivated by evidence that the IMM transmembrane potential Ψm, an important determinant of ETC activity, exhibits heterogeneity, i.e., a range of values, among a given local population of mitochondria. It specifically proposes that during oxygen limitation, Aβ selectively inactivates ETC complexes in mitochondria that exhibit relatively low absolute values of Ψm, thereby suppressing oxygen binding and consumption by complex IV of the ETC in these mitochondria. This effect of Aβ on low-Ψm mitochondria is hypothesized to spare hypoxia-limited oxygen for oxphos-enabling utilization by the ETC of the remaining active, higher-Ψm local mitochondria, and thereby to increase overall ATP generated collectively by the local mitochondrial population, i.e., to ameliorate hypoxia-induced oxphos reduction. The protective action of Aβ hypothesized here may slow the early development of hypoxia-associated cellular deterioration/loss in Alzheimer's disease and perhaps other neurodegenerative diseases.
    Keywords:  Alzheimer’s disease; amyloid-β; hypoxia; mitochondrial transmembrane potential; neurodegeneration; oxidative phosphorylation
  2. J Exp Biol. 2019 Oct 23. pii: jeb.208074. [Epub ahead of print]
    Gerber L, Clow KA, Katan T, Emam M, Leeuwis RHJ, Parrish CC, Gamperl AK.
      In fishes, the effect of O2 limitation on cardiac mitochondrial function remains largely unexplored. The sablefish (Anoplopoma fimbria) encounters considerable variations in environmental oxygen availability, and is an interesting model for studying the effects of hypoxia on fish cardiorespiratory function. We investigated how in vivo hypoxic acclimation (6 months at 40%+3 weeks at 20% air saturation) and in vitro anoxia-reoxygenation affected sablefish cardiac mitochondrial respiration and reactive oxygen species (ROS) release rates using high-resolution fluorespirometry. Further, we investigated how hypoxic acclimation affected the sensitivity of mitochondrial respiration to nitric oxide (NO), and compared mitochondrial lipid and fatty acid (FA) composition between groups. Hypoxic acclimation did not alter mitochondrial coupled or uncoupled respiration, or respiratory control ratio, ROS release rates, P50 or superoxide dismutase activity. However, it increased citrate synthase activity (by∼20%), increased the sensitivity of mitochondrial respiration to NO inhibition [i.e., the NO IC50 was 25% lower], and enhanced the recovery of respiration (by 21%) and reduced ROS release rates (by 25-30%) post-anoxia. Further, hypoxic acclimation altered the mitochondria's FA composition [increasing arachidonic acid (20:4ω6) and eicosapentaenoic acid (20:5ω3) proportions by 11 and 14%, respectively], and SIMPER analysis revealed that the phospholipid: sterol ratio was the largest contributor (24%) to the dissimilarity between treatments. Overall, these results suggest that hypoxic acclimation may protect sablefish cardiac bioenergetic function during or after periods of O2 limitation, and that this may be related to alterations in the mitochondria's sensitivity to NO and to adaptive changes in membrane composition (fluidity).
    Keywords:  Anoxia-Reoxygenation; Citrate Synthase; Fatty Acid Composition; Mitochondrial Respiration; Reactive Oxygen Species; Superoxide Dismutase.