Singleminded-2 Impacts Mitochondrial Networks and Mitophagy in C2C12 Myoblasts

Abstract

Mitophagy has become an increasingly important topic for addressing pathologies of neurodegenerative disease. Yet there is still much to be understood about the key players that regulate mitophagy as well as its involvement in other atrophic backgrounds. We have found that singleminded-2 (SIM2), a critical gene contributing to Down Syndrome pathologies, influences mitophagy and mitochondrial network remodeling of skeletal muscle myoblast cells. SIM2 is required for proper differentiation of myoblasts, and when lost, cells stop differentiation after gaining polarity. Although it is a transcription factor, it does not repress major myogenic factors. Rather, it localizes to mitochondria to modulate Parkin expression. This loss results in a decline in mitochondrial fusion proteins and branched mitochondrial networks critical for proper function of differentiated myotubes. Together this data suggests that SIM2 may play a bigger role in regulating homeostasis through metabolic functioning.