Chiang H.Ohno N.Hsieh Y.-L.Mahad D.J.Kikuchi S.Komuro H.SUNG-TSANG HSIEHTrapp B.D.2020-03-022020-03-0220150001-6322https://www.scopus.com/inward/record.uri?eid=2-s2.0-84938603886&doi=10.1007%2fs00401-014-1354-3&partnerID=40&md5=d6845e308b2273ee366b42b70958751ahttps://scholars.lib.ntu.edu.tw/handle/123456789/467735Capsaicin, 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 Ca2+ 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 Ca2+-dependent mitochondrial fission facilitates mitochondrial function and axonal survival following activation of axonal cationic channels. ? 2014, The Author(s).[SDGs]SDG3calcium ion; capsaicin; dynamin related protein 1; protein; unclassified drug; vanilloid receptor 1; vanilloid receptor 1 antagonist; calcium; capsaicin; TRPV1 protein, mouse; Trpv1 protein, rat; vanilloid receptor; animal cell; animal experiment; animal model; Article; axoplasm; capsaicin induced axonal degeneration; cell transport; controlled study; experimental neurologic disease; in vitro study; internal ribosome entry site; male; mitochondrial dynamics; mitochondrial fission; mitochondrial membrane potential; mitochondrial volume; mouse; nerve fiber; nerve fiber degeneration; neurofilament; nonhuman; nonmyelinated nerve; priority journal; protein expression; randomized controlled trial; rat; animal; axon; cell culture; chemically induced; drug effects; Institute for Cancer Research mouse; metabolism; mitochondrial dynamics; mitochondrion; nerve degeneration; pathology; pathophysiology; physiology; spinal ganglion; Sprague Dawley rat; Animals; Axons; Calcium; Capsaicin; Cells, Cultured; Ganglia, Spinal; Male; Membrane Potential, Mitochondrial; Mice, Inbred ICR; Mitochondria; Mitochondrial Dynamics; Nerve Degeneration; Rats, Sprague-Dawley; TRPV Cation Channelsjournal article10.1007/s00401-014-1354-3253228172-s2.0-84938603886