FIGURE 4.

Two hypothetical mechanisms of muscle fiber hypertrophy. In our proposed sarcoplasm expansion hypothesis of hypertrophy model, muscle fibers first grow through sarcoplasmic hypertrophy. This allows resident myonuclear domains to spatially, bioenergetically, and biosynthetically prepare for the accretion of additional myofibrils. Although resident domains may synthesize and accumulate some myofibril protein during this phase of hypertrophy, we hypothesize the predominance of sarcoplasmic hypertrophy reduces the transcriptional burden on resident domains. Once sarcoplasmic hypertrophy leads to appreciable cell growth, an additional myonuclear domain is acquired via satellite cell fusion. This new myonuclear domain can then appreciably contribute to myofibril protein accretion by “backfilling” space created through sarcoplasm expansion. In the myofibril expansion hypothesis of hypertrophy model, muscle fibers rapidly synthesize and accrue myofibril protein. This phenomenon leads to myofibril packing which acts to push the sarcolemma outward. Fibers eventually reach a size threshold, which leads to an additional myonuclear domain being acquired via satellite cell fusion. At this point both domains can operate to maintain and further synthesize new myofibrils.