Neurotrophins induce fission of mitochondria along embryonic sensory axons

eLife

Lorena Armijo-Weingart¹  Gianluca Gallo¹  Andrea Ketschek¹  Rajiv Sainath¹  Almudena Pacheco¹  George M Smith² 

[1] Department of Anatomy and Cell Biology, Shriner Hospitals Pediatric Research Center, Temple University Lewis Katz School of Medicine, Philadelphia, United States;Department of Neuroscience, Shriner Hospitals Pediatric Research Center, Temple University Lewis Katz School of Medicine, Philadelphia, United States;

关键词: axon;    Drp1;    fission;    branching;    ngf;    neurotrophins;   

DOI  :  10.7554/eLife.49494

来源: DOAJ

【 摘 要 】

Neurotrophins are growth factors that have a multitude of roles in the nervous system. We report that neurotrophins induce the fission of mitochondria along embryonic chick sensory axons driven by combined PI3K and Mek-Erk signaling. Following an initial burst of fission, a new steady state of neurotrophin-dependent mitochondria length is established. Mek-Erk controls the activity of the fission mediator Drp1 GTPase, while PI3K may contribute to the actin-dependent aspect of fission. Drp1-mediated fission is required for nerve growth factor (NGF)-induced collateral branching in vitro and expression of dominant negative Drp1 impairs the branching of axons in the developing spinal cord in vivo. Fission is also required for NGF-induced mitochondria-dependent intra-axonal translation of the actin regulatory protein cortactin, a previously determined component of NGF-induced branching. Collectively, these observations unveil a novel biological function of neurotrophins; the regulation of mitochondrial fission and steady state mitochondrial length and density in axons.

【 授权许可】

Unknown