Role of AMPK in regulation of LC3 lipidation as a marker of autophagy in skeletal muscle
During induction of the autophagosomal degradation process, LC3-I is lipidated to LC3-II and associates to the cargo isolation membrane allowing for autophagosome formation. Lipidation of LC3 results in an increased LC3-II/LC3-I ratio, and this ratio is an often used marker for autophagy in various...
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| Veröffentlicht in: | Cellular signalling 2016-06, Vol.28 (6), p.663-674 |
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| creator | Fritzen, Andreas Mæchel Frøsig, Christian Jeppesen, Jacob Jensen, Thomas Elbenhardt Lundsgaard, Anne-Marie Serup, Annette Karen Schjerling, Peter Proud, Chris G. Richter, Erik A. Kiens, Bente |
| description | During induction of the autophagosomal degradation process, LC3-I is lipidated to LC3-II and associates to the cargo isolation membrane allowing for autophagosome formation. Lipidation of LC3 results in an increased LC3-II/LC3-I ratio, and this ratio is an often used marker for autophagy in various tissues, including skeletal muscle. From cell studies AMPK has been proposed to be necessary and sufficient for LC3 lipidation. The aim of the present study was to investigate the role of AMPK in regulation of LC3 lipidation as a marker of autophagy in skeletal muscle. We observed an increase in the LC3-II/LC3-I ratio in skeletal muscle of AMPKα2 kinase-dead (KD) (p |
| doi_str_mv | 10.1016/j.cellsig.2016.03.005 |
| format | Article |
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•AMPKα2 is not necessary for induction of LC3 lipidation and autophagosome formation with fasting and aging.•LC3 lipidation is increased in muscle lacking functional AMPKα2 during fasting and aging.•Fasting-induced LC3 lipidation coincides with an initial decrease in plasma insulin and in muscle mTORC1 signaling.•Fasting-induced LC3 lipidation is not dependent on eEF2k, but is accompanied by increased levels of FoxO3a and ULK1.•LC3 lipidation seems not to be a universal response to muscle contraction in mice.]]></description><identifier>ISSN: 0898-6568</identifier><identifier>EISSN: 1873-3913</identifier><identifier>DOI: 10.1016/j.cellsig.2016.03.005</identifier><identifier>PMID: 26976209</identifier><language>eng</language><publisher>England: Elsevier Inc</publisher><subject>Aging ; Aging (artificial) ; Aging - physiology ; AMP-Activated Protein Kinases - genetics ; AMP-Activated Protein Kinases - metabolism ; AMP-Activated Protein Kinases - physiology ; AMPK ; Animals ; Autophagy ; Biomarkers ; Control ; Exercise and eEF2K ; Fasting ; Female ; Formations ; Gene Knock-In Techniques ; LC3 lipidation ; Lipid Metabolism ; Markers ; Mice ; Mice, Inbred C57BL ; Microtubule-Associated Proteins - metabolism ; Muscle Contraction ; Muscle, Skeletal - enzymology ; Muscle, Skeletal - metabolism ; Muscle, Skeletal - physiology ; Muscles ; Peptide Elongation Factor 2 - genetics ; Physical Conditioning, Animal ; Proteins ; Signal Transduction</subject><ispartof>Cellular signalling, 2016-06, Vol.28 (6), p.663-674</ispartof><rights>2016 Elsevier Inc.</rights><rights>Copyright © 2016 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c464t-4976b45be239b50f61e0366915561350727f904e8de4fe22200a80412c246a9b3</citedby><cites>FETCH-LOGICAL-c464t-4976b45be239b50f61e0366915561350727f904e8de4fe22200a80412c246a9b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.cellsig.2016.03.005$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26976209$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fritzen, Andreas Mæchel</creatorcontrib><creatorcontrib>Frøsig, Christian</creatorcontrib><creatorcontrib>Jeppesen, Jacob</creatorcontrib><creatorcontrib>Jensen, Thomas Elbenhardt</creatorcontrib><creatorcontrib>Lundsgaard, Anne-Marie</creatorcontrib><creatorcontrib>Serup, Annette Karen</creatorcontrib><creatorcontrib>Schjerling, Peter</creatorcontrib><creatorcontrib>Proud, Chris G.</creatorcontrib><creatorcontrib>Richter, Erik A.</creatorcontrib><creatorcontrib>Kiens, Bente</creatorcontrib><title>Role of AMPK in regulation of LC3 lipidation as a marker of autophagy in skeletal muscle</title><title>Cellular signalling</title><addtitle>Cell Signal</addtitle><description><![CDATA[During induction of the autophagosomal degradation process, LC3-I is lipidated to LC3-II and associates to the cargo isolation membrane allowing for autophagosome formation. Lipidation of LC3 results in an increased LC3-II/LC3-I ratio, and this ratio is an often used marker for autophagy in various tissues, including skeletal muscle. From cell studies AMPK has been proposed to be necessary and sufficient for LC3 lipidation. The aim of the present study was to investigate the role of AMPK in regulation of LC3 lipidation as a marker of autophagy in skeletal muscle. We observed an increase in the LC3-II/LC3-I ratio in skeletal muscle of AMPKα2 kinase-dead (KD) (p<0.001) and wild type (WT) (p<0.05) mice after 12h of fasting, which was greater (p<0.05) in AMPKα2 KD mice than in WT. The fasting-induced increase in the LC3-II/LC3-I ratio in both genotypes coincided with an initial decrease (p<0.01) in plasma insulin concentration, a subsequent decrease in muscle mTORC1 signaling and increased (p<0.05) levels of the autophagy-promoting proteins, FoxO3a and ULK1. Furthermore, a higher (p<0.01) LC3-II/LC3-I ratio was observed in old compared to young mice. We were not able to detect any change in LC3 lipidation with either in vivo treadmill exercise or in situ contractions. Collectively, these findings suggest that AMPKα2 is not necessary for induction of LC3 lipidation with fasting and aging. Furthermore, LC3 lipidation is increased in muscle lacking functional AMPKα2 during fasting and aging. Moreover, LC3 lipidation seems not to be a universal response to muscle contraction in mice.
•AMPKα2 is not necessary for induction of LC3 lipidation and autophagosome formation with fasting and aging.•LC3 lipidation is increased in muscle lacking functional AMPKα2 during fasting and aging.•Fasting-induced LC3 lipidation coincides with an initial decrease in plasma insulin and in muscle mTORC1 signaling.•Fasting-induced LC3 lipidation is not dependent on eEF2k, but is accompanied by increased levels of FoxO3a and ULK1.•LC3 lipidation seems not to be a universal response to muscle contraction in mice.]]></description><subject>Aging</subject><subject>Aging (artificial)</subject><subject>Aging - physiology</subject><subject>AMP-Activated Protein Kinases - genetics</subject><subject>AMP-Activated Protein Kinases - metabolism</subject><subject>AMP-Activated Protein Kinases - physiology</subject><subject>AMPK</subject><subject>Animals</subject><subject>Autophagy</subject><subject>Biomarkers</subject><subject>Control</subject><subject>Exercise and eEF2K</subject><subject>Fasting</subject><subject>Female</subject><subject>Formations</subject><subject>Gene Knock-In Techniques</subject><subject>LC3 lipidation</subject><subject>Lipid Metabolism</subject><subject>Markers</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microtubule-Associated Proteins - metabolism</subject><subject>Muscle Contraction</subject><subject>Muscle, Skeletal - enzymology</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscle, Skeletal - physiology</subject><subject>Muscles</subject><subject>Peptide Elongation Factor 2 - genetics</subject><subject>Physical Conditioning, Animal</subject><subject>Proteins</subject><subject>Signal Transduction</subject><issn>0898-6568</issn><issn>1873-3913</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtu2zAQRYmiRe08PiGFlt1IGT5FrorASNIgDhIUDZAdQUkjhw5tuaRUwH9fCXazzYqY4bkcziHkgkJBgarLdVFjCMmvCjaWBfACQH4ic6pLnnND-WcyB210rqTSM3KS0hqASlDsK5kxZUrFwMzJy68uYNa12dXD033mt1nE1RBc77vt1F0ueBb8zjeHjkuZyzYuvmGcbt3Qd7tXt9pPwfSGAXsXss2Q6oBn5EvrQsLz43lKnm-ufy9-5svH27vF1TKvhRJ9LsaPVEJWyLipJLSKInClDJVSUS6hZGVrQKBuULTIGANwGgRlNRPKmYqfku-Hd3ex-zNg6u3Gp0mN22I3JEs1VUC14PxjtCyN1lyrCZUHtI5dShFbu4t-XHxvKdjJv13bo387-bfA7eh_zH07jhiqDTbvqf_CR-DHAcDRyV-P0aba47bGxkese9t0_oMR_wCwMpYh</recordid><startdate>201606</startdate><enddate>201606</enddate><creator>Fritzen, Andreas Mæchel</creator><creator>Frøsig, Christian</creator><creator>Jeppesen, Jacob</creator><creator>Jensen, Thomas Elbenhardt</creator><creator>Lundsgaard, Anne-Marie</creator><creator>Serup, Annette Karen</creator><creator>Schjerling, Peter</creator><creator>Proud, Chris G.</creator><creator>Richter, Erik A.</creator><creator>Kiens, Bente</creator><general>Elsevier Inc</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>7X8</scope><scope>7U5</scope><scope>8FD</scope><scope>L7M</scope></search><sort><creationdate>201606</creationdate><title>Role of AMPK in regulation of LC3 lipidation as a marker of autophagy in skeletal muscle</title><author>Fritzen, Andreas Mæchel ; Frøsig, Christian ; Jeppesen, Jacob ; Jensen, Thomas Elbenhardt ; Lundsgaard, Anne-Marie ; Serup, Annette Karen ; Schjerling, Peter ; Proud, Chris G. ; Richter, Erik A. ; Kiens, Bente</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c464t-4976b45be239b50f61e0366915561350727f904e8de4fe22200a80412c246a9b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Aging</topic><topic>Aging (artificial)</topic><topic>Aging - physiology</topic><topic>AMP-Activated Protein Kinases - genetics</topic><topic>AMP-Activated Protein Kinases - metabolism</topic><topic>AMP-Activated Protein Kinases - physiology</topic><topic>AMPK</topic><topic>Animals</topic><topic>Autophagy</topic><topic>Biomarkers</topic><topic>Control</topic><topic>Exercise and eEF2K</topic><topic>Fasting</topic><topic>Female</topic><topic>Formations</topic><topic>Gene Knock-In Techniques</topic><topic>LC3 lipidation</topic><topic>Lipid Metabolism</topic><topic>Markers</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microtubule-Associated Proteins - metabolism</topic><topic>Muscle Contraction</topic><topic>Muscle, Skeletal - enzymology</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscle, Skeletal - physiology</topic><topic>Muscles</topic><topic>Peptide Elongation Factor 2 - genetics</topic><topic>Physical Conditioning, Animal</topic><topic>Proteins</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fritzen, Andreas Mæchel</creatorcontrib><creatorcontrib>Frøsig, Christian</creatorcontrib><creatorcontrib>Jeppesen, Jacob</creatorcontrib><creatorcontrib>Jensen, Thomas Elbenhardt</creatorcontrib><creatorcontrib>Lundsgaard, Anne-Marie</creatorcontrib><creatorcontrib>Serup, Annette Karen</creatorcontrib><creatorcontrib>Schjerling, Peter</creatorcontrib><creatorcontrib>Proud, Chris G.</creatorcontrib><creatorcontrib>Richter, Erik A.</creatorcontrib><creatorcontrib>Kiens, Bente</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Technology Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Cellular signalling</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fritzen, Andreas Mæchel</au><au>Frøsig, Christian</au><au>Jeppesen, Jacob</au><au>Jensen, Thomas Elbenhardt</au><au>Lundsgaard, Anne-Marie</au><au>Serup, Annette Karen</au><au>Schjerling, Peter</au><au>Proud, Chris G.</au><au>Richter, Erik A.</au><au>Kiens, Bente</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of AMPK in regulation of LC3 lipidation as a marker of autophagy in skeletal muscle</atitle><jtitle>Cellular signalling</jtitle><addtitle>Cell Signal</addtitle><date>2016-06</date><risdate>2016</risdate><volume>28</volume><issue>6</issue><spage>663</spage><epage>674</epage><pages>663-674</pages><issn>0898-6568</issn><eissn>1873-3913</eissn><abstract><![CDATA[During induction of the autophagosomal degradation process, LC3-I is lipidated to LC3-II and associates to the cargo isolation membrane allowing for autophagosome formation. Lipidation of LC3 results in an increased LC3-II/LC3-I ratio, and this ratio is an often used marker for autophagy in various tissues, including skeletal muscle. From cell studies AMPK has been proposed to be necessary and sufficient for LC3 lipidation. The aim of the present study was to investigate the role of AMPK in regulation of LC3 lipidation as a marker of autophagy in skeletal muscle. We observed an increase in the LC3-II/LC3-I ratio in skeletal muscle of AMPKα2 kinase-dead (KD) (p<0.001) and wild type (WT) (p<0.05) mice after 12h of fasting, which was greater (p<0.05) in AMPKα2 KD mice than in WT. The fasting-induced increase in the LC3-II/LC3-I ratio in both genotypes coincided with an initial decrease (p<0.01) in plasma insulin concentration, a subsequent decrease in muscle mTORC1 signaling and increased (p<0.05) levels of the autophagy-promoting proteins, FoxO3a and ULK1. Furthermore, a higher (p<0.01) LC3-II/LC3-I ratio was observed in old compared to young mice. We were not able to detect any change in LC3 lipidation with either in vivo treadmill exercise or in situ contractions. Collectively, these findings suggest that AMPKα2 is not necessary for induction of LC3 lipidation with fasting and aging. Furthermore, LC3 lipidation is increased in muscle lacking functional AMPKα2 during fasting and aging. Moreover, LC3 lipidation seems not to be a universal response to muscle contraction in mice.
•AMPKα2 is not necessary for induction of LC3 lipidation and autophagosome formation with fasting and aging.•LC3 lipidation is increased in muscle lacking functional AMPKα2 during fasting and aging.•Fasting-induced LC3 lipidation coincides with an initial decrease in plasma insulin and in muscle mTORC1 signaling.•Fasting-induced LC3 lipidation is not dependent on eEF2k, but is accompanied by increased levels of FoxO3a and ULK1.•LC3 lipidation seems not to be a universal response to muscle contraction in mice.]]></abstract><cop>England</cop><pub>Elsevier Inc</pub><pmid>26976209</pmid><doi>10.1016/j.cellsig.2016.03.005</doi><tpages>12</tpages></addata></record> |
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| subjects | Aging Aging (artificial) Aging - physiology AMP-Activated Protein Kinases - genetics AMP-Activated Protein Kinases - metabolism AMP-Activated Protein Kinases - physiology AMPK Animals Autophagy Biomarkers Control Exercise and eEF2K Fasting Female Formations Gene Knock-In Techniques LC3 lipidation Lipid Metabolism Markers Mice Mice, Inbred C57BL Microtubule-Associated Proteins - metabolism Muscle Contraction Muscle, Skeletal - enzymology Muscle, Skeletal - metabolism Muscle, Skeletal - physiology Muscles Peptide Elongation Factor 2 - genetics Physical Conditioning, Animal Proteins Signal Transduction |
| title | Role of AMPK in regulation of LC3 lipidation as a marker of autophagy in skeletal muscle |
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