Acyl-CoA thioesterase-2 facilitates mitochondrial fatty acid oxidation in the liver[S]
Acyl-CoA thioesterase (Acot)2 localizes to the mitochondrial matrix and hydrolyses long-chain fatty acyl-CoA into free FA and CoASH. Acot2 is expressed in highly oxidative tissues and is poised to modulate mitochondrial FA oxidation (FAO), yet its biological role is unknown. Using a model of adenov...
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doaj-3ac8167becda40619918c485afd4319d2021-04-28T06:01:13ZengElsevierJournal of Lipid Research0022-22752014-12-01551224582470Acyl-CoA thioesterase-2 facilitates mitochondrial fatty acid oxidation in the liver[S]Cynthia Moffat0Lavesh Bhatia1Teresa Nguyen2Peter Lynch3Miao Wang4Dongning Wang5Olga R. Ilkayeva6Xianlin Han7Matthew D. Hirschey8Steven M. Claypool9Erin L. Seifert10Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL 32827Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27710Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27710Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL 32827Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27710Department of Physiology, Johns Hopkins School of Medicine, Baltimore, MD 21205To whom correspondence should be addressed; Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107; To whom correspondence should be addressedAcyl-CoA thioesterase (Acot)2 localizes to the mitochondrial matrix and hydrolyses long-chain fatty acyl-CoA into free FA and CoASH. Acot2 is expressed in highly oxidative tissues and is poised to modulate mitochondrial FA oxidation (FAO), yet its biological role is unknown. Using a model of adenoviral Acot2 overexpression in mouse liver (Ad-Acot2), we show that Acot2 increases the utilization of FA substrate during the daytime in ad libitum-fed mice, but the nighttime switch to carbohydrate oxidation is similar to control mice. In further support of elevated FAO in Acot2 liver, daytime serum ketones were higher in Ad-Acot2 mice, and overnight fasting led to minimal hepatic steatosis as compared with control mice. In liver mitochondria from Ad-Acot2 mice, phosphorylating O2 consumption was higher with lipid substrate, but not with nonlipid substrate. This increase depended on whether FA could be activated on the outer mitochondrial membrane, suggesting that the FA released by Acot2 could be effluxed from mitochondria then taken back up again for oxidation. This circuit would prevent the build-up of inhibitory long-chain fatty acyl-CoA esters. Altogether, our findings indicate that Acot2 can enhance FAO, possibly by mitigating the accumulation of FAO intermediates within the mitochondrial matrix.http://www.sciencedirect.com/science/article/pii/S0022227520366864β-oxidationmitochondriamitochondrial thioesterasemitochondrial proton leakcardiolipinmouse |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Cynthia Moffat Lavesh Bhatia Teresa Nguyen Peter Lynch Miao Wang Dongning Wang Olga R. Ilkayeva Xianlin Han Matthew D. Hirschey Steven M. Claypool Erin L. Seifert |
spellingShingle |
Cynthia Moffat Lavesh Bhatia Teresa Nguyen Peter Lynch Miao Wang Dongning Wang Olga R. Ilkayeva Xianlin Han Matthew D. Hirschey Steven M. Claypool Erin L. Seifert Acyl-CoA thioesterase-2 facilitates mitochondrial fatty acid oxidation in the liver[S] Journal of Lipid Research β-oxidation mitochondria mitochondrial thioesterase mitochondrial proton leak cardiolipin mouse |
author_facet |
Cynthia Moffat Lavesh Bhatia Teresa Nguyen Peter Lynch Miao Wang Dongning Wang Olga R. Ilkayeva Xianlin Han Matthew D. Hirschey Steven M. Claypool Erin L. Seifert |
author_sort |
Cynthia Moffat |
title |
Acyl-CoA thioesterase-2 facilitates mitochondrial fatty acid oxidation in the liver[S] |
title_short |
Acyl-CoA thioesterase-2 facilitates mitochondrial fatty acid oxidation in the liver[S] |
title_full |
Acyl-CoA thioesterase-2 facilitates mitochondrial fatty acid oxidation in the liver[S] |
title_fullStr |
Acyl-CoA thioesterase-2 facilitates mitochondrial fatty acid oxidation in the liver[S] |
title_full_unstemmed |
Acyl-CoA thioesterase-2 facilitates mitochondrial fatty acid oxidation in the liver[S] |
title_sort |
acyl-coa thioesterase-2 facilitates mitochondrial fatty acid oxidation in the liver[s] |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2014-12-01 |
description |
Acyl-CoA thioesterase (Acot)2 localizes to the mitochondrial matrix and hydrolyses long-chain fatty acyl-CoA into free FA and CoASH. Acot2 is expressed in highly oxidative tissues and is poised to modulate mitochondrial FA oxidation (FAO), yet its biological role is unknown. Using a model of adenoviral Acot2 overexpression in mouse liver (Ad-Acot2), we show that Acot2 increases the utilization of FA substrate during the daytime in ad libitum-fed mice, but the nighttime switch to carbohydrate oxidation is similar to control mice. In further support of elevated FAO in Acot2 liver, daytime serum ketones were higher in Ad-Acot2 mice, and overnight fasting led to minimal hepatic steatosis as compared with control mice. In liver mitochondria from Ad-Acot2 mice, phosphorylating O2 consumption was higher with lipid substrate, but not with nonlipid substrate. This increase depended on whether FA could be activated on the outer mitochondrial membrane, suggesting that the FA released by Acot2 could be effluxed from mitochondria then taken back up again for oxidation. This circuit would prevent the build-up of inhibitory long-chain fatty acyl-CoA esters. Altogether, our findings indicate that Acot2 can enhance FAO, possibly by mitigating the accumulation of FAO intermediates within the mitochondrial matrix. |
topic |
β-oxidation mitochondria mitochondrial thioesterase mitochondrial proton leak cardiolipin mouse |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520366864 |
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