Plaat1 deficiency reduces cardiac cardiolipin content and impairs exercise tolerance
Phospholipase A and acyltransferase 1 (PLAAT1) catalyzes O-transacylase, N-transacylase, and phospholipase A1/2 reactions. We have demonstrated that PLAAT1 has O-transacylase activity in vitro using phosphatidylcholine as an acyl donor and monolysocardiolipin (MLCL) as an acyl acceptor, generating c...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227525000823 |
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| author | Ashkan Hashemi Ming Rong Liu John Z. Chan Antonia N. Berdeklis Alex D. Cocco Michelle V. Tomczewski Douglas Strathdee Ken D. Stark Robin E. Duncan |
| author_facet | Ashkan Hashemi Ming Rong Liu John Z. Chan Antonia N. Berdeklis Alex D. Cocco Michelle V. Tomczewski Douglas Strathdee Ken D. Stark Robin E. Duncan |
| author_sort | Ashkan Hashemi |
| collection | DOAJ |
| description | Phospholipase A and acyltransferase 1 (PLAAT1) catalyzes O-transacylase, N-transacylase, and phospholipase A1/2 reactions. We have demonstrated that PLAAT1 has O-transacylase activity in vitro using phosphatidylcholine as an acyl donor and monolysocardiolipin (MLCL) as an acyl acceptor, generating cardiolipin. However, a role for PLAAT1 in cardiolipin regulation in vivo has not yet been reported. We generated Plaat1-deficient (Plaat1−/−) mice and studied males and females for gross morphological differences, food intakes, respiratory gas exchange, total energy expenditure, and voluntary activity. We also evaluated cardiac cardiolipin contents, levels of mitochondrial proteins, and exercise capacity. Sex-matched Plaat1−/− mice had highly similar body weights to their wild-type (Wt) littermates, although male Plaat1−/− mice ate less. Male and female Plaat1−/− hearts were 14.2% and 10.6% smaller, respectively. Cardiac cardiolipin levels were ∼one-third lower in male and female Plaat1−/− mice compared to their sex-matched Wt littermates, largely due to lower cardiolipin linoleate. Levels of the mitochondrial protein succinate dehydrogenase complex flavoprotein subunit A were 13.8% and 16.3% lower in male and female Plaat1−/− mice, respectively. Both male and female Plaat1−/− mice had significantly lower oxygen consumption, carbon dioxide production, and total energy expenditure, and male Plaat1−/− mice had lower rearing activity than their sex-matched Wt littermates. While other measures of voluntary activity, including locomotion and ambulation did not differ significantly between genotypes, both males and females had reduced exercise tolerance. This work demonstrates a critical role for PLAAT1 in cardiac cardiolipin content and the regulation of energy metabolism and exercise tolerance in vivo. |
| format | Article |
| id | doaj-art-71205f12f86f407ba1269ed3c19e0e13 |
| institution | OA Journals |
| issn | 0022-2275 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj-art-71205f12f86f407ba1269ed3c19e0e132025-08-20T02:35:30ZengElsevierJournal of Lipid Research0022-22752025-06-0166610082210.1016/j.jlr.2025.100822Plaat1 deficiency reduces cardiac cardiolipin content and impairs exercise toleranceAshkan Hashemi0Ming Rong Liu1John Z. Chan2Antonia N. Berdeklis3Alex D. Cocco4Michelle V. Tomczewski5Douglas Strathdee6Ken D. Stark7Robin E. Duncan8University of Waterloo, Faculty of Health, Department of Kinesiology and Health Sciences, Waterloo, ON, CanadaUniversity of Waterloo, Faculty of Health, Department of Kinesiology and Health Sciences, Waterloo, ON, CanadaUniversity of Waterloo, Faculty of Health, Department of Kinesiology and Health Sciences, Waterloo, ON, CanadaUniversity of Waterloo, Faculty of Health, Department of Kinesiology and Health Sciences, Waterloo, ON, CanadaUniversity of Waterloo, Faculty of Health, Department of Kinesiology and Health Sciences, Waterloo, ON, CanadaUniversity of Waterloo, Faculty of Health, Department of Kinesiology and Health Sciences, Waterloo, ON, CanadaTransgenic Technology Laboratory, Cancer Research UK Beatson Institute, Glasgow, Scotland, UKUniversity of Waterloo, Faculty of Health, Department of Kinesiology and Health Sciences, Waterloo, ON, CanadaUniversity of Waterloo, Faculty of Health, Department of Kinesiology and Health Sciences, Waterloo, ON, Canada; For correspondence: Robin E. DuncanPhospholipase A and acyltransferase 1 (PLAAT1) catalyzes O-transacylase, N-transacylase, and phospholipase A1/2 reactions. We have demonstrated that PLAAT1 has O-transacylase activity in vitro using phosphatidylcholine as an acyl donor and monolysocardiolipin (MLCL) as an acyl acceptor, generating cardiolipin. However, a role for PLAAT1 in cardiolipin regulation in vivo has not yet been reported. We generated Plaat1-deficient (Plaat1−/−) mice and studied males and females for gross morphological differences, food intakes, respiratory gas exchange, total energy expenditure, and voluntary activity. We also evaluated cardiac cardiolipin contents, levels of mitochondrial proteins, and exercise capacity. Sex-matched Plaat1−/− mice had highly similar body weights to their wild-type (Wt) littermates, although male Plaat1−/− mice ate less. Male and female Plaat1−/− hearts were 14.2% and 10.6% smaller, respectively. Cardiac cardiolipin levels were ∼one-third lower in male and female Plaat1−/− mice compared to their sex-matched Wt littermates, largely due to lower cardiolipin linoleate. Levels of the mitochondrial protein succinate dehydrogenase complex flavoprotein subunit A were 13.8% and 16.3% lower in male and female Plaat1−/− mice, respectively. Both male and female Plaat1−/− mice had significantly lower oxygen consumption, carbon dioxide production, and total energy expenditure, and male Plaat1−/− mice had lower rearing activity than their sex-matched Wt littermates. While other measures of voluntary activity, including locomotion and ambulation did not differ significantly between genotypes, both males and females had reduced exercise tolerance. This work demonstrates a critical role for PLAAT1 in cardiac cardiolipin content and the regulation of energy metabolism and exercise tolerance in vivo.http://www.sciencedirect.com/science/article/pii/S0022227525000823cardiolipincell signalingglycerophospholipidsphospholipids/metabolismheartknockout mice |
| spellingShingle | Ashkan Hashemi Ming Rong Liu John Z. Chan Antonia N. Berdeklis Alex D. Cocco Michelle V. Tomczewski Douglas Strathdee Ken D. Stark Robin E. Duncan Plaat1 deficiency reduces cardiac cardiolipin content and impairs exercise tolerance Journal of Lipid Research cardiolipin cell signaling glycerophospholipids phospholipids/metabolism heart knockout mice |
| title | Plaat1 deficiency reduces cardiac cardiolipin content and impairs exercise tolerance |
| title_full | Plaat1 deficiency reduces cardiac cardiolipin content and impairs exercise tolerance |
| title_fullStr | Plaat1 deficiency reduces cardiac cardiolipin content and impairs exercise tolerance |
| title_full_unstemmed | Plaat1 deficiency reduces cardiac cardiolipin content and impairs exercise tolerance |
| title_short | Plaat1 deficiency reduces cardiac cardiolipin content and impairs exercise tolerance |
| title_sort | plaat1 deficiency reduces cardiac cardiolipin content and impairs exercise tolerance |
| topic | cardiolipin cell signaling glycerophospholipids phospholipids/metabolism heart knockout mice |
| url | http://www.sciencedirect.com/science/article/pii/S0022227525000823 |
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