Naked mole-rat skeletal muscle mitochondria exhibit minimal functional plasticity in acute or chronic hypoxia.

Abstract

Oxidative phosphorylation is compromised in hypoxia, but many organisms live and exercise in low oxygen environments. Hypoxia-driven adaptations at the mitochondrial level are common and may enhance energetic efficiency or minimize deleterious reactive oxygen species (ROS) generation. Mitochondria from various hypoxia-tolerant animals exhibit robust functional changes following in vivo hypoxia and we hypothesized that similar plasticity would occur in naked mole-rat skeletal muscle. To test this, we exposed adult subordinate naked mole-rats to normoxia (21% O2) or acute (4 h, 7% O2) or chronic hypoxia (4-6 weeks, 11% O2) and then isolated skeletal muscle mitochondria. Using high-resolution respirometry and a fluorescent indicator of ROS production, we then probed for changes in: i) lipid- (palmitoylcarnitine-malate), ii) carbohydrate- (pyruvate-malate), and iii) succinate-fueled metabolism, and also iv) complex IV electron transfer capacity, and v) H2O2 production. Compared to normoxic values, a) lipid-fueled uncoupled respiration was reduced ~15% during acute and chronic hypoxia, b) complex I-II capacity and the rate of ROS efflux were both unaffected, and c) complex II and IV uncoupled respiration were supressed ~16% following acute hypoxia. Notably, complex II-linked H2O2 efflux was 33% lower after acute hypoxia, which may reduce deleterious ROS bursts during reoxygenation. These mild changes in lipid- and carbohydrate-fueled respiratory capacity may reflect the need for this animal to exercise regularly in highly variable and intermittently hypoxic environments in which more robust plasticity may be energetically expensive.

• Authors: Hang Cheng, Daniel Munro, Kenny Huynh, Matthew E Pamenter
• Journal: Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology (Comp Biochem Physiol B Biochem Mol Biol) 2021 Aug-Sep Vol. 255 Pg. 110596 ISSN: 1879-1107 [Electronic] England
• PMID: 33757832 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Mitochondrial Proteins
• Reactive Oxygen Species
• Electron Transport Complex II
• Electron Transport Complex IV

Topics

• Acute Disease
• Animals
• Chronic Disease
• Electron Transport Complex II (metabolism)
• Electron Transport Complex IV (metabolism)
• Hypoxia (metabolism, pathology)
• Mitochondria, Muscle (metabolism, pathology)
• Mitochondrial Proteins (metabolism)
• Mole Rats
• Reactive Oxygen Species (metabolism)