The regulation, control, and consequences of mitochondrial oxygen utilization and disposition in the heart and skeletal muscle during hypoxia.
The major oxygen-dependent function of mitochondria partitions molecular oxygen between oxidative phosphorylation and reactive oxygen species generation. When oxygen becomes limiting, the modulation of mitochondrial function plays an important role in overall biologic adaptation. This review focuses on mitochondrial biology in the heart and skeletal muscle during hypoxia. The disparate mitochondrial responses discussed appear to be dependent on the degree of hypoxia, on the age at exposure to hypoxia, and on the duration of exposure. These hypoxia-induced changes include modulation in mitochondrial respiratory capacity; activation of the mitochondrial biogenesis regulatory program; induction of mitochondrial antioxidant defense systems; regulation of antiapoptotic mitochondrial proteins, and modulation of mitochondrial sensitivity to permeability transition. The mitochondria-derived reactive oxygen species signal-transduction events in response to hypoxia also are reviewed. The cardiac and skeletal muscle phenotypic signatures that result from mitochondrial adaptations include an amelioration of resistance to cardiac ischemia and modulations in exercise capacity and oxidative fuel preference. Overall, the data demonstrate the plasticity in mitochondrial regulation and function that facilitates adaptations to a limited oxygen supply. Moreover, data supporting the role of mitochondria as oxygen-sensing organelles, integrated into global cellular signal transduction are discussed.
Lynn
Edward G
EG
Cardiology Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892-1454, USA.
Lu
Zhongping
Z
Minerbi
Diane
D
Sack
Michael N
MN
D000818:Animals; D006706:Homeostasis; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008929:Mitochondria, Heart / Q000378:metabolism*; D008931:Mitochondria, Muscle / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption