FIGURE 17.

Muscle repair, regeneration, and refueling. A: multicellular interactions and intramyocellular processes that control muscle repair. Resident and infiltrating cells of different types are engaged by various signals in a temporally highly orchestrated manner. Thereby, damaged material is removed, muscle fibers repaired or de novo formed, and functional retrieval achieved. Activation of nociceptor signaling should prevent further exertion and damage during repair and regeneration. Moreover, the multicellular processes are complemented by intramyocellular pathways to restore membrane and sarcomere integrity as well as organelle function. B: postexercise refueling of glycogen, intramyocellular lipids (IMCL), and protein structures. Depleted intramyocellular energy substrate stores are replenished after exercise depending on a systemic, anabolic context, i.e., the availability of the corresponding substrates and signaling of anabolic hormones. Because of the energetic demand for protein, glycogen, and IMCL synthesis, these processes are coordinated with mitochondrial activity and ATP production. C: temporal specification of catabolic and anabolic processes by peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α). To avoid a futile cycle, the catabolic activity of PGC-1α during contractions must be separated from the anabolic function in regeneration. The mechanistic underpinnings of the transcriptional specification of this coactivator (and other regulators with multipurpose roles) remain unknown. FAP, fibro-adipogenic precursor; MG53, mitsugumin 53; mTOR, mammalian target of rapamycin; TF, transcription factor. Image created with BioRender.com, with permission.