Fin bud initiation factor homolog (Fibin) is a secreted protein that is relatively conserved among species. It is closely related to fin bud development and can regulate a variety of cellular processes. In our previous high-throughput chromosome conformation capture (Hi-C) study of pig embryonic muscle development, it was found that Fibin has high expression and activity during the development of pig primary muscle fibers. Therefore, we speculated Fibin participated in myogenesis severely. Specific deletion of Fibin in mouse skeletal muscle resulted in abnormal primary muscle fiber development during the embryonic period and a substantial decrease in skeletal muscle mass in adulthood. In vitro, knocking out Fibin in C2C12 cells promoted cell proliferation; however, after myogenic induction, cells lacking Fibin had almost no ability to differentiate into myotubes. During myogenic differentiation, loss of Fibin disrupts the normal function of mitochondria and impairs oxidative phosphorylation, resulting in decrease of NADH and FADH in the electron transport chain. Transmission electron microscopy also showed that mitochondrial morphology of Fibin-deficient C2C12 was impaired. In conclusion, our research has unveiled a novel mechanism of myogenesis regulation in mitochondrial function and potential target Fibin, and improved understanding of a broad range of mitochondrial muscle diseases.
Keywords: Fibin; Mitochondria; Myogenesis.
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