Looking Beyond Structure: Membrane Phospholipids of Skeletal Muscle Mitochondria

Skeletal muscle mitochondria are highly dynamic and are capable of tremendous expansion to meet cellular energetic demands. Such proliferation in mitochondrial mass requires a synchronized supply of enzymes and structural phospholipids. While transcriptional regulation of mitochondrial enzymes has been extensively studied, there is limited information on how mitochondrial membrane lipids are generated in skeletal muscle. Herein we describe how each class of phospholipids that constitute mitochondrial membranes are synthesized and/or imported, and summarize genetic evidence indicating that membrane phospholipid composition represents a significant modulator of skeletal muscle mitochondrial respiratory function. We also discuss how skeletal muscle mitochondrial phospholipids may mediate the effect of diet and exercise on oxidative metabolism.

TrendsThe strongest predictor of all-cause mortality is aerobic capacity, which is highly dependent on skeletal muscle mitochondrial function.Phospholipid composition of mitochondrial membranes modulates respiration through its effects on the activity of enzymes of the electron transport system (ETS), ultrastructure of cristae, and signaling for mitophagy, fusion, and fission.Clinical and experimental evidence links disruption of skeletal muscle mitochondrial phospholipid synthesis to functional defects and abnormal morphology, leading to myopathy, exercise intolerance, and shortened lifespan.The transcriptional control of mitochondrial enzymes has been well studied, but there is limited information on mechanisms that regulate mitochondrial phospholipid synthesis.