LonP1 regulates mitochondrial network remodeling through the PINK1/Parkin pathway during myoblast differentiation (Supplementary Table-1.docx)

Myoblast differentiation is a crucial process for
myogenesis. Mitochondria function as an energy-providing machine that is
critical to this process, and mitochondrial dysfunction can prevent myoblasts
from fusing into myotubes. However, the molecular mechanisms underlying the
dynamic regulation of mitochondrial networks remain poorly understood. In the
present study, we found that the PTEN induced kinase 1(PINK1) /Parkin (an E3
ubiquitin-protein ligase) pathway is activated at the early stage of myoblast
differentiation. Moreover, downregulation of mitofusin 2 (Mfn2) and increased
dynamin-related protein 1 (Drp1) resulted in loosely formed mitochondria during
this period. Furthermore, selective knockdown of the mitochondrial matrix
protein Lon proteinase-1 (LonP1) at the early stage of myoblast differentiation
induced mitochondrial depolarization and suppressed the PINK1/Parkin pathway and
reduced Mfn2 and Drp1 levels, which blocked mitochondrial remodeling and
myoblast differentiation. Overall, these data suggest that LonP1 plays an
essential role in maintaining the normal myoblast differentiation process,
which partly by regulating PINK1/Parkin mediated mitochondrial remodeling.