Live imaging reveals the cellular events downstream of SARM1 activation

SARM1 is an inducible NAD+ hydrolase that triggers axon loss and neuronal cell death in the injured and diseased nervous system. While SARM1 activation and enzyme function are well defined, the cellular events downstream of SARM1 activity but prior to axonal demise are much less well understood. Def...

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Autores principales:	Kwang Woo Ko, Laura Devault, Yo Sasaki, Jeffrey Milbrandt, Aaron DiAntonio
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	SARM1 calcium mitochondria NAD+ Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/4877f3da02fe49ecbeaf4ea689071126
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spelling	oai:doaj.org-article:4877f3da02fe49ecbeaf4ea6890711262021-11-24T15:32:04ZLive imaging reveals the cellular events downstream of SARM1 activation10.7554/eLife.711482050-084Xe71148https://doaj.org/article/4877f3da02fe49ecbeaf4ea6890711262021-11-01T00:00:00Zhttps://elifesciences.org/articles/71148https://doaj.org/toc/2050-084XSARM1 is an inducible NAD+ hydrolase that triggers axon loss and neuronal cell death in the injured and diseased nervous system. While SARM1 activation and enzyme function are well defined, the cellular events downstream of SARM1 activity but prior to axonal demise are much less well understood. Defects in calcium, mitochondria, ATP, and membrane homeostasis occur in injured axons, but the relationships among these events have been difficult to disentangle because prior studies analyzed large collections of axons in which cellular events occur asynchronously. Here, we used live imaging of mouse sensory neurons with single axon resolution to investigate the cellular events downstream of SARM1 activity. Our studies support a model in which SARM1 NADase activity leads to an ordered sequence of events from loss of cellular ATP, to defects in mitochondrial movement and depolarization, followed by calcium influx, externalization of phosphatidylserine, and loss of membrane permeability prior to catastrophic axonal self-destruction.Kwang Woo KoLaura DevaultYo SasakiJeffrey MilbrandtAaron DiAntonioeLife Sciences Publications LtdarticleSARM1calciummitochondriaNAD+MedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SARM1 calcium mitochondria NAD+ Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	SARM1 calcium mitochondria NAD+ Medicine R Science Q Biology (General) QH301-705.5 Kwang Woo Ko Laura Devault Yo Sasaki Jeffrey Milbrandt Aaron DiAntonio Live imaging reveals the cellular events downstream of SARM1 activation
description	SARM1 is an inducible NAD+ hydrolase that triggers axon loss and neuronal cell death in the injured and diseased nervous system. While SARM1 activation and enzyme function are well defined, the cellular events downstream of SARM1 activity but prior to axonal demise are much less well understood. Defects in calcium, mitochondria, ATP, and membrane homeostasis occur in injured axons, but the relationships among these events have been difficult to disentangle because prior studies analyzed large collections of axons in which cellular events occur asynchronously. Here, we used live imaging of mouse sensory neurons with single axon resolution to investigate the cellular events downstream of SARM1 activity. Our studies support a model in which SARM1 NADase activity leads to an ordered sequence of events from loss of cellular ATP, to defects in mitochondrial movement and depolarization, followed by calcium influx, externalization of phosphatidylserine, and loss of membrane permeability prior to catastrophic axonal self-destruction.
format	article
author	Kwang Woo Ko Laura Devault Yo Sasaki Jeffrey Milbrandt Aaron DiAntonio
author_facet	Kwang Woo Ko Laura Devault Yo Sasaki Jeffrey Milbrandt Aaron DiAntonio
author_sort	Kwang Woo Ko
title	Live imaging reveals the cellular events downstream of SARM1 activation
title_short	Live imaging reveals the cellular events downstream of SARM1 activation
title_full	Live imaging reveals the cellular events downstream of SARM1 activation
title_fullStr	Live imaging reveals the cellular events downstream of SARM1 activation
title_full_unstemmed	Live imaging reveals the cellular events downstream of SARM1 activation
title_sort	live imaging reveals the cellular events downstream of sarm1 activation
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/4877f3da02fe49ecbeaf4ea689071126
work_keys_str_mv	AT kwangwooko liveimagingrevealsthecellulareventsdownstreamofsarm1activation AT lauradevault liveimagingrevealsthecellulareventsdownstreamofsarm1activation AT yosasaki liveimagingrevealsthecellulareventsdownstreamofsarm1activation AT jeffreymilbrandt liveimagingrevealsthecellulareventsdownstreamofsarm1activation AT aarondiantonio liveimagingrevealsthecellulareventsdownstreamofsarm1activation
_version_	1718414926304772096

Live imaging reveals the cellular events downstream of SARM1 activation

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