Somatic autophagy of axonal mitochondria in ischemic neurons
Mitophagy protects against ischemic neuronal injury by eliminating damaged mitochondria, but it is unclear how mitochondria in distal axons are cleared. We find that oxygen and glucose deprivation-reperfusion reduces mitochondrial content in both cell bodies and axons. Axonal mitochondria eliminatio...
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| Veröffentlicht in: | The Journal of cell biology 2019-06, Vol.218 (6), p.1891-1907 |
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| container_title | The Journal of cell biology |
| container_volume | 218 |
| creator | Zheng, Yanrong Zhang, Xiangnan Wu, Xiaoli Jiang, Lei Ahsan, Anil Ma, Shijia Xiao, Ziyu Han, Feng Qin, Zheng-Hong Hu, Weiwei Chen, Zhong |
| description | Mitophagy protects against ischemic neuronal injury by eliminating damaged mitochondria, but it is unclear how mitochondria in distal axons are cleared. We find that oxygen and glucose deprivation-reperfusion reduces mitochondrial content in both cell bodies and axons. Axonal mitochondria elimination was not abolished in
;nes-
neurons, suggesting the absence of direct mitophagy in axons. Instead, axonal mitochondria were enwrapped by autophagosomes in soma and axon-derived mitochondria prioritized for elimination by autophagy. Intriguingly, axonal mitochondria showed prompt loss of anterograde motility but increased retrograde movement upon reperfusion. Anchoring of axonal mitochondria by syntaphilin blocked neuronal mitophagy and aggravated injury. Conversely, induced binding of mitochondria to dynein reinforced retrograde transport and enhanced mitophagy to prevent mitochondrial dysfunction and attenuate neuronal injury. Therefore, we reveal somatic autophagy of axonal mitochondria in ischemic neurons and establish a direct link of retrograde mitochondrial movement with mitophagy. Our findings may provide a new concept for reducing ischemic neuronal injury by correcting mitochondrial motility. |
| doi_str_mv | 10.1083/jcb.201804101 |
| format | Article |
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;nes-
neurons, suggesting the absence of direct mitophagy in axons. Instead, axonal mitochondria were enwrapped by autophagosomes in soma and axon-derived mitochondria prioritized for elimination by autophagy. Intriguingly, axonal mitochondria showed prompt loss of anterograde motility but increased retrograde movement upon reperfusion. Anchoring of axonal mitochondria by syntaphilin blocked neuronal mitophagy and aggravated injury. Conversely, induced binding of mitochondria to dynein reinforced retrograde transport and enhanced mitophagy to prevent mitochondrial dysfunction and attenuate neuronal injury. Therefore, we reveal somatic autophagy of axonal mitochondria in ischemic neurons and establish a direct link of retrograde mitochondrial movement with mitophagy. Our findings may provide a new concept for reducing ischemic neuronal injury by correcting mitochondrial motility.</description><identifier>ISSN: 0021-9525</identifier><identifier>EISSN: 1540-8140</identifier><identifier>DOI: 10.1083/jcb.201804101</identifier><identifier>PMID: 30979799</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Anchoring ; Animals ; Autophagy ; Autophagy-Related Protein 7 - physiology ; Axons ; Axons - metabolism ; Axons - pathology ; Brain Ischemia - metabolism ; Brain Ischemia - pathology ; Cerebral Cortex - metabolism ; Cerebral Cortex - pathology ; Deprivation ; Dynein ; Injury prevention ; Ischemia ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Mice ; Mice, Knockout ; Mitochondria ; Mitochondria - metabolism ; Mitochondria - pathology ; Mitophagy ; Motility ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Neurons ; Neurons - metabolism ; Neurons - pathology ; Phagocytosis ; Phagosomes ; Reperfusion ; Retrograde transport ; Ubiquitin-Protein Ligases - physiology</subject><ispartof>The Journal of cell biology, 2019-06, Vol.218 (6), p.1891-1907</ispartof><rights>2019 Zheng et al.</rights><rights>Copyright Rockefeller University Press Jun 2019</rights><rights>2019 Zheng et al. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c481t-2a904431104c97dd377af2a39e5ec9d36e4d4a5a8e7c7cffb073bae292956dfe3</citedby><cites>FETCH-LOGICAL-c481t-2a904431104c97dd377af2a39e5ec9d36e4d4a5a8e7c7cffb073bae292956dfe3</cites><orcidid>0000-0003-4755-9357 ; 0000-0002-7603-7403</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30979799$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zheng, Yanrong</creatorcontrib><creatorcontrib>Zhang, Xiangnan</creatorcontrib><creatorcontrib>Wu, Xiaoli</creatorcontrib><creatorcontrib>Jiang, Lei</creatorcontrib><creatorcontrib>Ahsan, Anil</creatorcontrib><creatorcontrib>Ma, Shijia</creatorcontrib><creatorcontrib>Xiao, Ziyu</creatorcontrib><creatorcontrib>Han, Feng</creatorcontrib><creatorcontrib>Qin, Zheng-Hong</creatorcontrib><creatorcontrib>Hu, Weiwei</creatorcontrib><creatorcontrib>Chen, Zhong</creatorcontrib><title>Somatic autophagy of axonal mitochondria in ischemic neurons</title><title>The Journal of cell biology</title><addtitle>J Cell Biol</addtitle><description>Mitophagy protects against ischemic neuronal injury by eliminating damaged mitochondria, but it is unclear how mitochondria in distal axons are cleared. We find that oxygen and glucose deprivation-reperfusion reduces mitochondrial content in both cell bodies and axons. Axonal mitochondria elimination was not abolished in
;nes-
neurons, suggesting the absence of direct mitophagy in axons. Instead, axonal mitochondria were enwrapped by autophagosomes in soma and axon-derived mitochondria prioritized for elimination by autophagy. Intriguingly, axonal mitochondria showed prompt loss of anterograde motility but increased retrograde movement upon reperfusion. Anchoring of axonal mitochondria by syntaphilin blocked neuronal mitophagy and aggravated injury. Conversely, induced binding of mitochondria to dynein reinforced retrograde transport and enhanced mitophagy to prevent mitochondrial dysfunction and attenuate neuronal injury. Therefore, we reveal somatic autophagy of axonal mitochondria in ischemic neurons and establish a direct link of retrograde mitochondrial movement with mitophagy. Our findings may provide a new concept for reducing ischemic neuronal injury by correcting mitochondrial motility.</description><subject>Anchoring</subject><subject>Animals</subject><subject>Autophagy</subject><subject>Autophagy-Related Protein 7 - physiology</subject><subject>Axons</subject><subject>Axons - metabolism</subject><subject>Axons - pathology</subject><subject>Brain Ischemia - metabolism</subject><subject>Brain Ischemia - pathology</subject><subject>Cerebral Cortex - metabolism</subject><subject>Cerebral Cortex - pathology</subject><subject>Deprivation</subject><subject>Dynein</subject><subject>Injury prevention</subject><subject>Ischemia</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mitochondria</subject><subject>Mitochondria - metabolism</subject><subject>Mitochondria - pathology</subject><subject>Mitophagy</subject><subject>Motility</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Neurons</subject><subject>Neurons - metabolism</subject><subject>Neurons - pathology</subject><subject>Phagocytosis</subject><subject>Phagosomes</subject><subject>Reperfusion</subject><subject>Retrograde transport</subject><subject>Ubiquitin-Protein Ligases - physiology</subject><issn>0021-9525</issn><issn>1540-8140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkMtLw0AQhxdRbK0evUrAc-rsI48FEaT4goIH9bxMNptmS5Otu4nY_97UalHmMIf5-M3MR8g5hSmFnF8tdTFlQHMQFOgBGdNEQJxTAYdkDMBoLBOWjMhJCEsAEJngx2TEQWZDyTG5fnENdlZH2HduXeNiE7kqwk_X4ipqbOd07drSW4xsG9mga9MMcGt679pwSo4qXAVz9tMn5O3-7nX2GM-fH55mt_NYi5x2MUMJQnBKQWiZlSXPMqwYcmkSo2XJUyNKgQnmJtOZrqoCMl6gYZLJJC0rwyfkZpe77ovGlNq0nceVWnvboN8oh1b9n7S2Vgv3odJEbFUMAZc_Ad699yZ0aul6P7wYFGNc0pTl31S8o7R3IXhT7TdQUFvZapCt9rIH_uLvWXv61y7_Ar4Ke74</recordid><startdate>20190603</startdate><enddate>20190603</enddate><creator>Zheng, Yanrong</creator><creator>Zhang, Xiangnan</creator><creator>Wu, Xiaoli</creator><creator>Jiang, Lei</creator><creator>Ahsan, Anil</creator><creator>Ma, Shijia</creator><creator>Xiao, Ziyu</creator><creator>Han, Feng</creator><creator>Qin, Zheng-Hong</creator><creator>Hu, Weiwei</creator><creator>Chen, Zhong</creator><general>Rockefeller University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4755-9357</orcidid><orcidid>https://orcid.org/0000-0002-7603-7403</orcidid></search><sort><creationdate>20190603</creationdate><title>Somatic autophagy of axonal mitochondria in ischemic neurons</title><author>Zheng, Yanrong ; Zhang, Xiangnan ; Wu, Xiaoli ; Jiang, Lei ; Ahsan, Anil ; Ma, Shijia ; Xiao, Ziyu ; Han, Feng ; Qin, Zheng-Hong ; Hu, Weiwei ; Chen, Zhong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c481t-2a904431104c97dd377af2a39e5ec9d36e4d4a5a8e7c7cffb073bae292956dfe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Anchoring</topic><topic>Animals</topic><topic>Autophagy</topic><topic>Autophagy-Related Protein 7 - physiology</topic><topic>Axons</topic><topic>Axons - metabolism</topic><topic>Axons - pathology</topic><topic>Brain Ischemia - metabolism</topic><topic>Brain Ischemia - pathology</topic><topic>Cerebral Cortex - metabolism</topic><topic>Cerebral Cortex - pathology</topic><topic>Deprivation</topic><topic>Dynein</topic><topic>Injury prevention</topic><topic>Ischemia</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mitochondria</topic><topic>Mitochondria - metabolism</topic><topic>Mitochondria - pathology</topic><topic>Mitophagy</topic><topic>Motility</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Neurons</topic><topic>Neurons - metabolism</topic><topic>Neurons - pathology</topic><topic>Phagocytosis</topic><topic>Phagosomes</topic><topic>Reperfusion</topic><topic>Retrograde transport</topic><topic>Ubiquitin-Protein Ligases - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zheng, Yanrong</creatorcontrib><creatorcontrib>Zhang, Xiangnan</creatorcontrib><creatorcontrib>Wu, Xiaoli</creatorcontrib><creatorcontrib>Jiang, Lei</creatorcontrib><creatorcontrib>Ahsan, Anil</creatorcontrib><creatorcontrib>Ma, Shijia</creatorcontrib><creatorcontrib>Xiao, Ziyu</creatorcontrib><creatorcontrib>Han, Feng</creatorcontrib><creatorcontrib>Qin, Zheng-Hong</creatorcontrib><creatorcontrib>Hu, Weiwei</creatorcontrib><creatorcontrib>Chen, Zhong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zheng, Yanrong</au><au>Zhang, Xiangnan</au><au>Wu, Xiaoli</au><au>Jiang, Lei</au><au>Ahsan, Anil</au><au>Ma, Shijia</au><au>Xiao, Ziyu</au><au>Han, Feng</au><au>Qin, Zheng-Hong</au><au>Hu, Weiwei</au><au>Chen, Zhong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Somatic autophagy of axonal mitochondria in ischemic neurons</atitle><jtitle>The Journal of cell biology</jtitle><addtitle>J Cell Biol</addtitle><date>2019-06-03</date><risdate>2019</risdate><volume>218</volume><issue>6</issue><spage>1891</spage><epage>1907</epage><pages>1891-1907</pages><issn>0021-9525</issn><eissn>1540-8140</eissn><abstract>Mitophagy protects against ischemic neuronal injury by eliminating damaged mitochondria, but it is unclear how mitochondria in distal axons are cleared. We find that oxygen and glucose deprivation-reperfusion reduces mitochondrial content in both cell bodies and axons. Axonal mitochondria elimination was not abolished in
;nes-
neurons, suggesting the absence of direct mitophagy in axons. Instead, axonal mitochondria were enwrapped by autophagosomes in soma and axon-derived mitochondria prioritized for elimination by autophagy. Intriguingly, axonal mitochondria showed prompt loss of anterograde motility but increased retrograde movement upon reperfusion. Anchoring of axonal mitochondria by syntaphilin blocked neuronal mitophagy and aggravated injury. Conversely, induced binding of mitochondria to dynein reinforced retrograde transport and enhanced mitophagy to prevent mitochondrial dysfunction and attenuate neuronal injury. Therefore, we reveal somatic autophagy of axonal mitochondria in ischemic neurons and establish a direct link of retrograde mitochondrial movement with mitophagy. Our findings may provide a new concept for reducing ischemic neuronal injury by correcting mitochondrial motility.</abstract><cop>United States</cop><pub>Rockefeller University Press</pub><pmid>30979799</pmid><doi>10.1083/jcb.201804101</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0003-4755-9357</orcidid><orcidid>https://orcid.org/0000-0002-7603-7403</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Anchoring Animals Autophagy Autophagy-Related Protein 7 - physiology Axons Axons - metabolism Axons - pathology Brain Ischemia - metabolism Brain Ischemia - pathology Cerebral Cortex - metabolism Cerebral Cortex - pathology Deprivation Dynein Injury prevention Ischemia Membrane Proteins - genetics Membrane Proteins - metabolism Mice Mice, Knockout Mitochondria Mitochondria - metabolism Mitochondria - pathology Mitophagy Motility Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Neurons Neurons - metabolism Neurons - pathology Phagocytosis Phagosomes Reperfusion Retrograde transport Ubiquitin-Protein Ligases - physiology |
| title | Somatic autophagy of axonal mitochondria in ischemic neurons |
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