High-level dynein impairs mitochondrial distribution and differentiation of rhabdomyosarcoma cells

Background Rhabdomyosarcoma (RMS) is a rare disease that affects children and young adults. Two major subtypes of RMS, namely embryonal RMS (eRMS) and alveolar RMS (aRMS), are defective in myoblast differentiation and fusion. During myoblast differentiation, mitochondria undergo morphology change and metabolic program shift. This study is aim to investigate the role of mitochondria in RMS differentiation defect. Results In this study, we demonstrate that the mitochondria of RD and RH30 cells are enlarged and have a perinuclear distribution. Because impaired mitochondrial morphology, trafficking, and activity have been implicated in many human diseases, any link between these phenotypes and their causal relationship with physiological outcomes is important. We found that RD cells had reduced levels of the myosin motor MYO19 and elevated levels of the dynein motor and MIRO1/2 adaptors. This suggests that a loss of local actin-based anterograde transport and a simultaneous increase in microtubule-based retrograde transport is responsible for the perinuclear mitochondrial distribution. MYO19 overexpression and dynein inhibition were each able to partially rescue this phenotype, and dynein inhibition rescued myoblast fusion. Conclusions The results of this study reveal a novel link between mitochondrial distribution and myoblast fusion. We showed that a reduction in MYO19-mediated anterograde local transport of mitochondria combined with an increase in dynein-mediated retrograde transport resulted in perinuclear clustering of mitochondria and impaired myoblast fusion during differentiation.