Microtubules coordinate mitochondria transport with myofibril morphogenesis during muscle development

Abstract

Muscle morphogenesis creates highly specialised muscle cells containing contractile myofibrils and energy producing mitochondria. Myofibrils are chains of sarcomeres, whose myosin motors slide over actin filaments at the expense of ATP. Thus, myofibrils and mitochondria are in intimate contact in mature muscles. However, how mitochondria morphogenesis is coordinated with myofibrillogenesis during development remains largely unknown. Here, we used in vivo imaging to investigate myofibril and mitochondria network dynamics in developing Drosophila flight muscles. We found that mitochondria rapidly intercalate from the surface of actin bundles to their interior; concomitantly, actin filaments condense to individual myofibrils. This ensures that mitochondria are in intimate proximity to each myofibril. Interestingly, antiparallel microtubules bundle in concert with the assembling myofibrils, suggesting a key role in myofibril orientation. Indeed, light-induced microtubule severing directly affects myofibril orientation, whereas knock-down of kinesin heavy chain specifically blocks mitochondria intercalation and long-range transport. Importantly, mitochondria-myofibril intercalation and microtubule-based transport of mitochondria is conserved in developing mammalian muscle. Together, these data identify a key role for microtubules in coordinating mitochondria and myofibril morphogenesis to build functional muscles.