title: Mitochondrial fission augments capsaicin-induced axonal degeneration.
abstract: Capsaicin, an agonist of transient receptor potential vanilloid receptor 1, induces axonal degeneration of peripheral sensory nerves and is commonly used to treat painful sensory neuropathies. In this study, we investigated the role of mitochondrial dynamics in capsaicin-induced axonal degeneration. In capsaicin-treated rodent sensory axons, axonal swellings, decreased mitochondrial stationary site length and reduced mitochondrial transport preceded axonal degeneration. Increased axoplasmic Ca(2+) mediated the alterations in mitochondrial length and transport. While sustaining mitochondrial transport did not reduce axonal swellings in capsaicin-treated axons, preventing mitochondrial fission by overexpression of mutant dynamin-related protein 1 increased mitochondrial length, retained mitochondrial membrane potentials and reduced axonal loss upon capsaicin treatment. These results establish that mitochondrial stationary site size significantly affects axonal integrity and suggest that inhibition of Ca(2+)-dependent mitochondrial fission facilitates mitochondrial function and axonal survival following activation of axonal cationic channels.
authors.affiliation: Department of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, 10051, Taiwan.
authors.forename: Hao
authors.initials: H
authors.lastname: Chiang
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Ohno
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Hsieh
authors.forename: Don J
authors.initials: DJ
authors.lastname: Mahad
authors.forename: Shin
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Komuro
authors.forename: Sung-Tsang
authors.initials: ST
authors.lastname: Hsieh
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Trapp
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000633:toxicity*; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D063154:Mitochondrial Dynamics / Q000187:drug effects* / Q000502:physiology; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000378:metabolism
chemical_list: D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C493922:Trpv1 protein, rat; D002211:Capsaicin; D002118:Calcium