Dynamic adaptation of liver mitochondria to chronic alcohol feeding in mice: biogenesis, remodeling, and functional alterations
Liver mitochondria undergo dynamic alterations following chronic alcohol feeding to mice. Intragastric alcohol feeding to mice resulted in 1) increased state III respiration (109% compared with control) in isolated liver mitochondria, probably due to increased levels of complexes I, IV, and V being...
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| Veröffentlicht in: | The Journal of biological chemistry 2012-12, Vol.287 (50), p.42165-42179 |
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| creator | Han, Derick Ybanez, Maria D Johnson, Heather S McDonald, Jeniece N Mesropyan, Lusine Sancheti, Harsh Martin, Gary Martin, Alanna Lim, Atalie M Dara, Lily Cadenas, Enrique Tsukamoto, Hidekazu Kaplowitz, Neil |
| description | Liver mitochondria undergo dynamic alterations following chronic alcohol feeding to mice. Intragastric alcohol feeding to mice resulted in 1) increased state III respiration (109% compared with control) in isolated liver mitochondria, probably due to increased levels of complexes I, IV, and V being incorporated into the respiratory chain; 2) increased mitochondrial NAD(+) and NADH levels (∼2-fold), with no change in the redox status; 3) alteration in mitochondrial morphology, with increased numbers of elongated mitochondria; and 4) enhanced mitochondrial biogenesis in the liver, which corresponded with an up-regulation of PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α). Oral alcohol feeding to mice, which is associated with less liver injury and steatosis, slightly enhanced respiration in isolated liver mitochondria (30.8% compared with control), lower than the striking increase caused by intragastric alcohol feeding. Mitochondrial respiration increased with both oral and intragastric alcohol feeding despite extensive N-acetylation of mitochondrial proteins. The alcohol-induced mitochondrial alterations are probably an adaptive response to enhance alcohol metabolism in the liver. Isolated liver mitochondria from alcohol-treated mice had a greater rate of acetaldehyde metabolism and respiration when treated with acetaldehyde than control. Aldehyde dehydrogenase-2 levels were unaltered in response to alcohol, suggesting that the greater acetaldehyde metabolism by isolated mitochondria from alcohol-treated mice was due to increased mitochondrial respiration that regenerated NAD(+), the rate-limiting substrate in alcohol/acetaldehyde metabolism. Overall, our work suggests that mitochondrial plasticity in the liver may be an important adaptive response to the metabolic stress caused by alcohol intake and could potentially play a role in many other vital functions performed by the liver. |
| doi_str_mv | 10.1074/jbc.M112.377374 |
| format | Article |
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Intragastric alcohol feeding to mice resulted in 1) increased state III respiration (109% compared with control) in isolated liver mitochondria, probably due to increased levels of complexes I, IV, and V being incorporated into the respiratory chain; 2) increased mitochondrial NAD(+) and NADH levels (∼2-fold), with no change in the redox status; 3) alteration in mitochondrial morphology, with increased numbers of elongated mitochondria; and 4) enhanced mitochondrial biogenesis in the liver, which corresponded with an up-regulation of PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α). Oral alcohol feeding to mice, which is associated with less liver injury and steatosis, slightly enhanced respiration in isolated liver mitochondria (30.8% compared with control), lower than the striking increase caused by intragastric alcohol feeding. Mitochondrial respiration increased with both oral and intragastric alcohol feeding despite extensive N-acetylation of mitochondrial proteins. The alcohol-induced mitochondrial alterations are probably an adaptive response to enhance alcohol metabolism in the liver. Isolated liver mitochondria from alcohol-treated mice had a greater rate of acetaldehyde metabolism and respiration when treated with acetaldehyde than control. Aldehyde dehydrogenase-2 levels were unaltered in response to alcohol, suggesting that the greater acetaldehyde metabolism by isolated mitochondria from alcohol-treated mice was due to increased mitochondrial respiration that regenerated NAD(+), the rate-limiting substrate in alcohol/acetaldehyde metabolism. Overall, our work suggests that mitochondrial plasticity in the liver may be an important adaptive response to the metabolic stress caused by alcohol intake and could potentially play a role in many other vital functions performed by the liver.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M112.377374</identifier><identifier>PMID: 23086958</identifier><language>eng</language><publisher>United States: American Society for Biochemistry and Molecular Biology</publisher><subject>Acetaldehyde - metabolism ; Acetylation - drug effects ; Adaptation, Physiological - drug effects ; Alcohol Drinking - adverse effects ; Alcohol Drinking - metabolism ; Alcohol Drinking - pathology ; Aldehyde Dehydrogenase - metabolism ; Aldehyde Dehydrogenase, Mitochondrial ; Animals ; Central Nervous System Depressants - adverse effects ; Central Nervous System Depressants - pharmacology ; Electron Transport Chain Complex Proteins - metabolism ; Ethanol - adverse effects ; Ethanol - pharmacology ; Liver - metabolism ; Liver - pathology ; Male ; Mice ; Microbiology ; Mitochondria, Liver - metabolism ; Mitochondria, Liver - pathology ; NAD - metabolism ; Oxygen Consumption - drug effects ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Stress, Physiological - drug effects ; Trans-Activators - biosynthesis ; Transcription Factors ; Up-Regulation - drug effects</subject><ispartof>The Journal of biological chemistry, 2012-12, Vol.287 (50), p.42165-42179</ispartof><rights>2012 by The American Society for Biochemistry and Molecular Biology, Inc. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3516762/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3516762/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23086958$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Han, Derick</creatorcontrib><creatorcontrib>Ybanez, Maria D</creatorcontrib><creatorcontrib>Johnson, Heather S</creatorcontrib><creatorcontrib>McDonald, Jeniece N</creatorcontrib><creatorcontrib>Mesropyan, Lusine</creatorcontrib><creatorcontrib>Sancheti, Harsh</creatorcontrib><creatorcontrib>Martin, Gary</creatorcontrib><creatorcontrib>Martin, Alanna</creatorcontrib><creatorcontrib>Lim, Atalie M</creatorcontrib><creatorcontrib>Dara, Lily</creatorcontrib><creatorcontrib>Cadenas, Enrique</creatorcontrib><creatorcontrib>Tsukamoto, Hidekazu</creatorcontrib><creatorcontrib>Kaplowitz, Neil</creatorcontrib><title>Dynamic adaptation of liver mitochondria to chronic alcohol feeding in mice: biogenesis, remodeling, and functional alterations</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Liver mitochondria undergo dynamic alterations following chronic alcohol feeding to mice. Intragastric alcohol feeding to mice resulted in 1) increased state III respiration (109% compared with control) in isolated liver mitochondria, probably due to increased levels of complexes I, IV, and V being incorporated into the respiratory chain; 2) increased mitochondrial NAD(+) and NADH levels (∼2-fold), with no change in the redox status; 3) alteration in mitochondrial morphology, with increased numbers of elongated mitochondria; and 4) enhanced mitochondrial biogenesis in the liver, which corresponded with an up-regulation of PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α). Oral alcohol feeding to mice, which is associated with less liver injury and steatosis, slightly enhanced respiration in isolated liver mitochondria (30.8% compared with control), lower than the striking increase caused by intragastric alcohol feeding. Mitochondrial respiration increased with both oral and intragastric alcohol feeding despite extensive N-acetylation of mitochondrial proteins. The alcohol-induced mitochondrial alterations are probably an adaptive response to enhance alcohol metabolism in the liver. Isolated liver mitochondria from alcohol-treated mice had a greater rate of acetaldehyde metabolism and respiration when treated with acetaldehyde than control. Aldehyde dehydrogenase-2 levels were unaltered in response to alcohol, suggesting that the greater acetaldehyde metabolism by isolated mitochondria from alcohol-treated mice was due to increased mitochondrial respiration that regenerated NAD(+), the rate-limiting substrate in alcohol/acetaldehyde metabolism. Overall, our work suggests that mitochondrial plasticity in the liver may be an important adaptive response to the metabolic stress caused by alcohol intake and could potentially play a role in many other vital functions performed by the liver.</description><subject>Acetaldehyde - metabolism</subject><subject>Acetylation - drug effects</subject><subject>Adaptation, Physiological - drug effects</subject><subject>Alcohol Drinking - adverse effects</subject><subject>Alcohol Drinking - metabolism</subject><subject>Alcohol Drinking - pathology</subject><subject>Aldehyde Dehydrogenase - metabolism</subject><subject>Aldehyde Dehydrogenase, Mitochondrial</subject><subject>Animals</subject><subject>Central Nervous System Depressants - adverse effects</subject><subject>Central Nervous System Depressants - pharmacology</subject><subject>Electron Transport Chain Complex Proteins - metabolism</subject><subject>Ethanol - adverse effects</subject><subject>Ethanol - pharmacology</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Male</subject><subject>Mice</subject><subject>Microbiology</subject><subject>Mitochondria, Liver - metabolism</subject><subject>Mitochondria, Liver - pathology</subject><subject>NAD - metabolism</subject><subject>Oxygen Consumption - drug effects</subject><subject>Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha</subject><subject>Stress, Physiological - drug effects</subject><subject>Trans-Activators - biosynthesis</subject><subject>Transcription Factors</subject><subject>Up-Regulation - drug effects</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkEtLw0AUhQdRbK2u3cn8AFNnMq_EhSD1CRU3Cu7CPG6aKclMSdJCV_51U1_o3ZzFOee7cBA6pWRKieIXS2OnT5SmU6YUU3wPjSnJWMIEfdtHY0JSmuSpyEboqOuWZDie00M0ShnJZC6yMXq_2QbdeIu106te9z4GHEtc-w20uPF9tFUMrvUa9xHbqo1hl61trGKNSwDnwwL7MEQtXGLj4wICdL47xy000UE9-OdYB4fLdbA7vK6Hfg_t56_uGB2Uuu7g5Fsn6PXu9mX2kMyf7x9n1_NklUrZJwCWZlw4EJnQlFNi0pwRwxRwx4TJwRpnZCkpFYRxxTICSjJmNAcrM16yCbr64q7WpgFnIfStrotV6xvdbouoffHfCb4qFnFTDFNKJdMBcPYX8Nv8mZJ9AHngemk</recordid><startdate>20121207</startdate><enddate>20121207</enddate><creator>Han, Derick</creator><creator>Ybanez, Maria D</creator><creator>Johnson, Heather S</creator><creator>McDonald, Jeniece N</creator><creator>Mesropyan, Lusine</creator><creator>Sancheti, Harsh</creator><creator>Martin, Gary</creator><creator>Martin, Alanna</creator><creator>Lim, Atalie M</creator><creator>Dara, Lily</creator><creator>Cadenas, Enrique</creator><creator>Tsukamoto, Hidekazu</creator><creator>Kaplowitz, Neil</creator><general>American Society for Biochemistry and Molecular Biology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>5PM</scope></search><sort><creationdate>20121207</creationdate><title>Dynamic adaptation of liver mitochondria to chronic alcohol feeding in mice: biogenesis, remodeling, and functional alterations</title><author>Han, Derick ; Ybanez, Maria D ; Johnson, Heather S ; McDonald, Jeniece N ; Mesropyan, Lusine ; Sancheti, Harsh ; Martin, Gary ; Martin, Alanna ; Lim, Atalie M ; Dara, Lily ; Cadenas, Enrique ; Tsukamoto, Hidekazu ; Kaplowitz, Neil</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p266t-eec1845de585a1410b2930b37e4d35b9ecbdb6f61150347380e7633ba4ec684f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Acetaldehyde - metabolism</topic><topic>Acetylation - drug effects</topic><topic>Adaptation, Physiological - drug effects</topic><topic>Alcohol Drinking - adverse effects</topic><topic>Alcohol Drinking - metabolism</topic><topic>Alcohol Drinking - pathology</topic><topic>Aldehyde Dehydrogenase - metabolism</topic><topic>Aldehyde Dehydrogenase, Mitochondrial</topic><topic>Animals</topic><topic>Central Nervous System Depressants - adverse effects</topic><topic>Central Nervous System Depressants - pharmacology</topic><topic>Electron Transport Chain Complex Proteins - metabolism</topic><topic>Ethanol - adverse effects</topic><topic>Ethanol - pharmacology</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Male</topic><topic>Mice</topic><topic>Microbiology</topic><topic>Mitochondria, Liver - metabolism</topic><topic>Mitochondria, Liver - pathology</topic><topic>NAD - metabolism</topic><topic>Oxygen Consumption - drug effects</topic><topic>Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha</topic><topic>Stress, Physiological - drug effects</topic><topic>Trans-Activators - biosynthesis</topic><topic>Transcription Factors</topic><topic>Up-Regulation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Han, Derick</creatorcontrib><creatorcontrib>Ybanez, Maria D</creatorcontrib><creatorcontrib>Johnson, Heather S</creatorcontrib><creatorcontrib>McDonald, Jeniece N</creatorcontrib><creatorcontrib>Mesropyan, Lusine</creatorcontrib><creatorcontrib>Sancheti, Harsh</creatorcontrib><creatorcontrib>Martin, Gary</creatorcontrib><creatorcontrib>Martin, Alanna</creatorcontrib><creatorcontrib>Lim, Atalie M</creatorcontrib><creatorcontrib>Dara, Lily</creatorcontrib><creatorcontrib>Cadenas, Enrique</creatorcontrib><creatorcontrib>Tsukamoto, Hidekazu</creatorcontrib><creatorcontrib>Kaplowitz, Neil</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Han, Derick</au><au>Ybanez, Maria D</au><au>Johnson, Heather S</au><au>McDonald, Jeniece N</au><au>Mesropyan, Lusine</au><au>Sancheti, Harsh</au><au>Martin, Gary</au><au>Martin, Alanna</au><au>Lim, Atalie M</au><au>Dara, Lily</au><au>Cadenas, Enrique</au><au>Tsukamoto, Hidekazu</au><au>Kaplowitz, Neil</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dynamic adaptation of liver mitochondria to chronic alcohol feeding in mice: biogenesis, remodeling, and functional alterations</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2012-12-07</date><risdate>2012</risdate><volume>287</volume><issue>50</issue><spage>42165</spage><epage>42179</epage><pages>42165-42179</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Liver mitochondria undergo dynamic alterations following chronic alcohol feeding to mice. Intragastric alcohol feeding to mice resulted in 1) increased state III respiration (109% compared with control) in isolated liver mitochondria, probably due to increased levels of complexes I, IV, and V being incorporated into the respiratory chain; 2) increased mitochondrial NAD(+) and NADH levels (∼2-fold), with no change in the redox status; 3) alteration in mitochondrial morphology, with increased numbers of elongated mitochondria; and 4) enhanced mitochondrial biogenesis in the liver, which corresponded with an up-regulation of PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α). Oral alcohol feeding to mice, which is associated with less liver injury and steatosis, slightly enhanced respiration in isolated liver mitochondria (30.8% compared with control), lower than the striking increase caused by intragastric alcohol feeding. Mitochondrial respiration increased with both oral and intragastric alcohol feeding despite extensive N-acetylation of mitochondrial proteins. The alcohol-induced mitochondrial alterations are probably an adaptive response to enhance alcohol metabolism in the liver. Isolated liver mitochondria from alcohol-treated mice had a greater rate of acetaldehyde metabolism and respiration when treated with acetaldehyde than control. Aldehyde dehydrogenase-2 levels were unaltered in response to alcohol, suggesting that the greater acetaldehyde metabolism by isolated mitochondria from alcohol-treated mice was due to increased mitochondrial respiration that regenerated NAD(+), the rate-limiting substrate in alcohol/acetaldehyde metabolism. Overall, our work suggests that mitochondrial plasticity in the liver may be an important adaptive response to the metabolic stress caused by alcohol intake and could potentially play a role in many other vital functions performed by the liver.</abstract><cop>United States</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>23086958</pmid><doi>10.1074/jbc.M112.377374</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acetaldehyde - metabolism Acetylation - drug effects Adaptation, Physiological - drug effects Alcohol Drinking - adverse effects Alcohol Drinking - metabolism Alcohol Drinking - pathology Aldehyde Dehydrogenase - metabolism Aldehyde Dehydrogenase, Mitochondrial Animals Central Nervous System Depressants - adverse effects Central Nervous System Depressants - pharmacology Electron Transport Chain Complex Proteins - metabolism Ethanol - adverse effects Ethanol - pharmacology Liver - metabolism Liver - pathology Male Mice Microbiology Mitochondria, Liver - metabolism Mitochondria, Liver - pathology NAD - metabolism Oxygen Consumption - drug effects Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Stress, Physiological - drug effects Trans-Activators - biosynthesis Transcription Factors Up-Regulation - drug effects |
| title | Dynamic adaptation of liver mitochondria to chronic alcohol feeding in mice: biogenesis, remodeling, and functional alterations |
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