HSPD1 Regulates C2C12 Cell Proliferation and Differentiation in Association With Mitochondrial Function Changes

HSPD1 is an important chaperone protein whose primary function is to assist the correct folding of mitochondrial proteins and its co-chaperone. It exerts multiple biological effects, including participation in protein homeostasis maintenance, stress resistance, and cellular protection. However, whether Hspd1 modulates the proliferation and differentiation of C2C12 cells remains unclear. In this study, we observed that overexpression or knockdown of the Hspd1 gene increased or decreased C2C12 cell proliferation, respectively, whereas differentiation exhibited the opposite trend. Furthermore, co-immunoprecipitation coupled with mass spectrometry identified several putative HSPD1-interacting partners. Functional assays revealed that altering Hspd1 expression correlated with changes in the expression of mitochondrial morphology-related genes, transcripts of components of the tricarboxylic acid cycle and electron transport chain, as well as intracellular ATP levels. Although these results are consistent with the hypothesis that HSPD1-associated mitochondrial alterations may contribute to myoblast behavior, they do not exclude other potential mechanisms. Collectively, this study provides correlative evidence linking Hspd1 to mitochondrial regulation in C2C12 cells and underscores the necessity for further mechanistic dissection, including rescue experiments to establish causality.