摘要
Rare disease rhabdomyosarcoma-derived RD cells and RH30 cells are defective in myogenesis. In this study, we demonstrate that mitochondria in these cells are enlarged and display a perinuclear distribution. Given that impaired mitochondrial morphology, trafficking, and activity are implicated in many human diseases, characterizing the link between these phenotypes and their physiological outcomes is essential. We found that RD cells had reduced levels of the myosin motor MYO19 and elevated levels of the dynein motor and MIRO1/2 adaptors. Our findings indicate that impaired local actin-based anterograde transport, together with enhanced microtubule-based retrograde transport, drives this perinuclear mitochondrial clustering. Overexpression of MYO19 in RD cells partially rescued this phenotype, while dynein inhibition altered mitochondrial distribution and restored myogenic differentiation in both RD and RH30 cells. Collectively, these findings reveal an intricate interplay among mitochondrial morphology, distribution, and myoblast fusion that underlies both normal physiology and disease.
[Display omitted]
•Mitochondria in human rhabdomyosarcoma (RMS) cells cluster at perinuclear region•RMS cells exhibit reduced myosin motor MYO19 and impaired actin-based anterograde•High level dynein in RMS cells increase retrograde transport of mitochondria•Inhibiting dynein rescues myogenic differentiation defect of RMS cells
Molecular biology; Cell biology; Specialized functions of cells