Edit Publication: Cheng 2021 Comp Biochem Physiol B Biochem Mol Biol

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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% O<sub>2</sub>) or acute (4 h, 7% O<sub>2</sub>) or chronic hypoxia (4-6 weeks, 11% O<sub>2</sub>) 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'') H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub> 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.
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MiPareas:	Gender Respiration Instruments;methods mt-Biogenesis;mt-density mt-Structure;fission;fusion mt-Membrane mtDNA;mt-genetics nDNA;cell genetics Genetic knockout;overexpression Comparative MiP;environmental MiP Developmental biology Exercise physiology;nutrition;life style mt-Medicine Patients Pharmacology;toxicology mt-Awareness
Pathological states:	COPD Aging;senescence Alzheimer's Autism Cancer Cardiovascular Diabetes Inherited Infectious Myopathy Neurodegenerative Obesity Parkinson's Sepsis Other
Stress conditions:	Hypoxia Cell death Cryopreservation Ischemia-reperfusion Permeability transition Oxidative stress;RONS Temperature Mitochondrial disease
Organism:	Pig Human Mouse Rat Guinea pig Bovines Horse Dog Rabbit Cat Other mammals Chicken Zebrafish Drosophila Artemia Caenorhabditis elegans Saccharomyces cerevisiae Birds Reptiles Amphibians Fishes Chelicerates Crustaceans Hexapods Myriapods Annelids Molluscs Nematodes Other invertebrates Fungi Plants Protists Eubacteria Archea Algae
Tissues;cells:	Fat Heart Skeletal muscle Nervous system Liver Kidney Lung;gill Islet cell;pancreas;thymus Endothelial;epithelial;mesothelial cell Blood cells Genital Other cell lines CHO HEK HeLa Neuroblastoma Fibroblast HUVEC Macrophage-derived Lymphocyte Platelet Stem cells
Preparations:	SMP Intact organism Intact organ Permeabilized cells Permeabilized tissue Homogenate Isolated mitochondria Chloroplasts Enzyme Oxidase;biochemical oxidation Intact cells
Enzyme:	Complex I Adenine nucleotide translocase Complex II;succinate dehydrogenase Complex III Complex IV;cytochrome c oxidase Complex V;ATP synthase Inner mt-membrane transporter Marker enzyme Supercomplex TCA cycle and matrix dehydrogenases Uncoupling protein
Regulation; kinetics:	pH Aerobic glycolysis ADP ATP ATP production AMP Calcium Coupling efficiency;uncoupling Cyt c Flux control Inhibitor Ion;substrate transport mt-Membrane potential Oxygen kinetics PCr;Cr Phosphate Redox state Substrate Temperature Threshold;excess capacity Uncoupler Fatty acid Amino acid Q-junction effect
Coupling:	ET LEAK ROUTINE OXPHOS
Pathways:	F N S Gp DQ CIV NS Other combinations ROX
High-resolution respirometry:	pH Oxygraph-2k TIP2k O2k-Fluorometer NO TPP Ca O2k-Spectrophotometer O2k-Manual O2k-Protocol Theory NextGen-O2k
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