Figure 1.

Exercise training–induced mitochondrial adaptation in skeletal muscle. Exercise stimulates PGC-1α activity and expression, which promotes mitochondrial biogenesis, mainly by coordinating the transcriptions in the nuclear genome (through interaction with NRF1/2) and the mitochondrial genome (through transcription of the TFAM gene). The new, healthy mitochondria (green) likely fuse with (mitochondrial fusion) and the old, damaged mitochondria (red) likely separate from (mitochondrial fission) the mitochondrial reticulum. Exercise promotes both fusion (through OPA1 and MFN1/2) and fission (through MFF1 and DRP1) of IMM, OMM, and content. Damaged mitochondria, presumably due to the loss of mitochondrial membrane potential, can be recognized by autophagy machinery through the autophagy proteins MAP1LC3, PINK/PARKIN/p62, NIX/BNIP3, and FUNDC1 acting alone or in combination. At the same time, exercise leads to sequential activation of ULK1 and BECLIN1 and their downstream effectors to promote phagophore formation, which engulfs the damaged mitochondria to form an autophagosome. Fusion of the autophagosome with the lysosome completes the mitochondrial life cycle. Exercise training improves mitochondrial quantity through mitochondrial biogenesis and mitochondrial quality through a combination of mitochondrial biogenesis, dynamics, and mitophagy. Mitochondrial color change denotes quality from green, indicative of good quality, to red, indicative poor quality.