Resistin destroys mitochondrial biogenesis by inhibiting the PGC-1α/ NRF1/TFAM signaling pathway
Mitochondrial biogenesis deficits in neuronal cells are associated with the pathological progression of neurodegenerative diseases. Resistin, a secretory adipocytokine, possesses multiple physiological functions in diverse cells and tissues. However, the effects of resistin on mitochondrial biogenes...
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Veröffentlicht in: | Biochemical and biophysical research communications 2018-09, Vol.504 (1), p.13-18 |
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description | Mitochondrial biogenesis deficits in neuronal cells are associated with the pathological progression of neurodegenerative diseases. Resistin, a secretory adipocytokine, possesses multiple physiological functions in diverse cells and tissues. However, the effects of resistin on mitochondrial biogenesis in neuronal cells are still elusive. In the current study, we found that resistin caused a sustainable decrease in mitochondrial contents, including mitochondrial DNA/nuclear DNA ratio (mtDNA/nDNA), mitochondrial mass, cytochrome b protein expression, and cytochrome c oxidase activity, which were correlated with “loss of mitochondrial function” including reduced mitochondrial respiration rate and ATP production in human SH-SY5Y neuronal cells. Indeed, resistin treatment destroyed the expression of peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α), a master regulator of mitochondrial biogenesis, as well as its downstream target genes including nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM). Notably, overexpression of PGC-1α could completely rescue mitochondrial biogenesis and mitochondrial deficits induced by resistin. Mechanistically, inhibition of 5′-adenosine monophosphate-activated protein kinase (AMPK) was shown to mediate the inhibitory effects of resistin on mitochondrial biogenesis.
•Resistin caused impairment of mitochondrial biogenesis in neuronal cells.•Resistin induced loss of mitochondrial function by reducing respiration rate and ATP.•Resistin inhibited the PGC-1α/NRF1/TFAM pathway.•PGC-1α abolished the inhibitory effects of resistin in mitochondrial biogenesis. |
doi_str_mv | 10.1016/j.bbrc.2018.08.027 |
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•Resistin caused impairment of mitochondrial biogenesis in neuronal cells.•Resistin induced loss of mitochondrial function by reducing respiration rate and ATP.•Resistin inhibited the PGC-1α/NRF1/TFAM pathway.•PGC-1α abolished the inhibitory effects of resistin in mitochondrial biogenesis.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2018.08.027</identifier><identifier>PMID: 30172371</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; ADENOSINE ; CYTOCHROMES ; MITOCHONDRIA ; Mitochondrial biogenesis ; mtDNA ; NERVOUS SYSTEM DISEASES ; Neurodegenerative diseases ; OXIDASES ; Peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α) ; RECEPTORS ; Resistin ; TRANSCRIPTION FACTORS</subject><ispartof>Biochemical and biophysical research communications, 2018-09, Vol.504 (1), p.13-18</ispartof><rights>2018</rights><rights>Copyright © 2018. Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-37a54152ba0ceccf40666200837a26b098e3a95a24b3a0692e17951f624e1cf33</citedby><cites>FETCH-LOGICAL-c384t-37a54152ba0ceccf40666200837a26b098e3a95a24b3a0692e17951f624e1cf33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2018.08.027$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30172371$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/23103546$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Zhenbo</creatorcontrib><creatorcontrib>Tao, Shanwei</creatorcontrib><creatorcontrib>Li, Xiaohui</creatorcontrib><creatorcontrib>Yao, Qinghe</creatorcontrib><title>Resistin destroys mitochondrial biogenesis by inhibiting the PGC-1α/ NRF1/TFAM signaling pathway</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Mitochondrial biogenesis deficits in neuronal cells are associated with the pathological progression of neurodegenerative diseases. Resistin, a secretory adipocytokine, possesses multiple physiological functions in diverse cells and tissues. However, the effects of resistin on mitochondrial biogenesis in neuronal cells are still elusive. In the current study, we found that resistin caused a sustainable decrease in mitochondrial contents, including mitochondrial DNA/nuclear DNA ratio (mtDNA/nDNA), mitochondrial mass, cytochrome b protein expression, and cytochrome c oxidase activity, which were correlated with “loss of mitochondrial function” including reduced mitochondrial respiration rate and ATP production in human SH-SY5Y neuronal cells. Indeed, resistin treatment destroyed the expression of peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α), a master regulator of mitochondrial biogenesis, as well as its downstream target genes including nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM). Notably, overexpression of PGC-1α could completely rescue mitochondrial biogenesis and mitochondrial deficits induced by resistin. Mechanistically, inhibition of 5′-adenosine monophosphate-activated protein kinase (AMPK) was shown to mediate the inhibitory effects of resistin on mitochondrial biogenesis.
•Resistin caused impairment of mitochondrial biogenesis in neuronal cells.•Resistin induced loss of mitochondrial function by reducing respiration rate and ATP.•Resistin inhibited the PGC-1α/NRF1/TFAM pathway.•PGC-1α abolished the inhibitory effects of resistin in mitochondrial biogenesis.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>ADENOSINE</subject><subject>CYTOCHROMES</subject><subject>MITOCHONDRIA</subject><subject>Mitochondrial biogenesis</subject><subject>mtDNA</subject><subject>NERVOUS SYSTEM DISEASES</subject><subject>Neurodegenerative diseases</subject><subject>OXIDASES</subject><subject>Peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α)</subject><subject>RECEPTORS</subject><subject>Resistin</subject><subject>TRANSCRIPTION FACTORS</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp9kc9u00AQxleIiqaFF-CALHHh4mRm115nJS5VRApSW1BVJG6r9Xocb-R4w64DymP1RfpMrJXCEWmkOcxvvvnzMfYWYY6AcrGd13Wwcw64nEMKXr1gMwQFOUcoXrIZAMicK_xxzi5i3AIgFlK9YucCsOKiwhkz9xRdHN2QNRTH4I8x27nR284PTXCmz2rnNzRMUFYfMzd0rnYJ32RjR9m361WOT4-L7O5-jYuH9dVtFt1mMP0E7M3Y_TbH1-ysNX2kN8_5kn1ff3pYfc5vvl5_WV3d5FYsizEXlSkLLHltwJK1bQFSSg6wTAUua1BLEkaVhhe1MCAVJ6xUia3kBaFthbhk70-6Pp2jo3Uj2c76YSA7ai4QRFnIRH04Ufvgfx7SyXrnoqW-NwP5Q9QclII0GzCh_ITa4GMM1Op9cDsTjhpBTwborZ4M0JMBGlLwKjW9e9Y_1Dtq_rX8_XgCPp4ASr_45ShMq9JgqXFh2rTx7n_6fwBQN5WS</recordid><startdate>20180926</startdate><enddate>20180926</enddate><creator>Chen, Zhenbo</creator><creator>Tao, Shanwei</creator><creator>Li, Xiaohui</creator><creator>Yao, Qinghe</creator><general>Elsevier Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>OTOTI</scope></search><sort><creationdate>20180926</creationdate><title>Resistin destroys mitochondrial biogenesis by inhibiting the PGC-1α/ NRF1/TFAM signaling pathway</title><author>Chen, Zhenbo ; Tao, Shanwei ; Li, Xiaohui ; Yao, Qinghe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-37a54152ba0ceccf40666200837a26b098e3a95a24b3a0692e17951f624e1cf33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>ADENOSINE</topic><topic>CYTOCHROMES</topic><topic>MITOCHONDRIA</topic><topic>Mitochondrial biogenesis</topic><topic>mtDNA</topic><topic>NERVOUS SYSTEM DISEASES</topic><topic>Neurodegenerative diseases</topic><topic>OXIDASES</topic><topic>Peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α)</topic><topic>RECEPTORS</topic><topic>Resistin</topic><topic>TRANSCRIPTION FACTORS</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Zhenbo</creatorcontrib><creatorcontrib>Tao, Shanwei</creatorcontrib><creatorcontrib>Li, Xiaohui</creatorcontrib><creatorcontrib>Yao, Qinghe</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Zhenbo</au><au>Tao, Shanwei</au><au>Li, Xiaohui</au><au>Yao, Qinghe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Resistin destroys mitochondrial biogenesis by inhibiting the PGC-1α/ NRF1/TFAM signaling pathway</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2018-09-26</date><risdate>2018</risdate><volume>504</volume><issue>1</issue><spage>13</spage><epage>18</epage><pages>13-18</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Mitochondrial biogenesis deficits in neuronal cells are associated with the pathological progression of neurodegenerative diseases. Resistin, a secretory adipocytokine, possesses multiple physiological functions in diverse cells and tissues. However, the effects of resistin on mitochondrial biogenesis in neuronal cells are still elusive. In the current study, we found that resistin caused a sustainable decrease in mitochondrial contents, including mitochondrial DNA/nuclear DNA ratio (mtDNA/nDNA), mitochondrial mass, cytochrome b protein expression, and cytochrome c oxidase activity, which were correlated with “loss of mitochondrial function” including reduced mitochondrial respiration rate and ATP production in human SH-SY5Y neuronal cells. Indeed, resistin treatment destroyed the expression of peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α), a master regulator of mitochondrial biogenesis, as well as its downstream target genes including nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM). Notably, overexpression of PGC-1α could completely rescue mitochondrial biogenesis and mitochondrial deficits induced by resistin. Mechanistically, inhibition of 5′-adenosine monophosphate-activated protein kinase (AMPK) was shown to mediate the inhibitory effects of resistin on mitochondrial biogenesis.
•Resistin caused impairment of mitochondrial biogenesis in neuronal cells.•Resistin induced loss of mitochondrial function by reducing respiration rate and ATP.•Resistin inhibited the PGC-1α/NRF1/TFAM pathway.•PGC-1α abolished the inhibitory effects of resistin in mitochondrial biogenesis.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>30172371</pmid><doi>10.1016/j.bbrc.2018.08.027</doi><tpages>6</tpages></addata></record> |
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subjects | 60 APPLIED LIFE SCIENCES ADENOSINE CYTOCHROMES MITOCHONDRIA Mitochondrial biogenesis mtDNA NERVOUS SYSTEM DISEASES Neurodegenerative diseases OXIDASES Peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α) RECEPTORS Resistin TRANSCRIPTION FACTORS |
title | Resistin destroys mitochondrial biogenesis by inhibiting the PGC-1α/ NRF1/TFAM signaling pathway |
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