SOD2 in skeletal muscle: New insights from an inducible deletion model
Metabolic conditions such as obesity, insulin resistance and glucose intolerance are frequently associated with impairments in skeletal muscle function and metabolism. This is often linked to dysregulation of homeostatic pathways including an increase in reactive oxygen species (ROS) and oxidative s...
Main Authors: | , , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Elsevier
2021-11-01
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Series: | Redox Biology |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231721002949 |
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doaj-ae96313ccf2649e18f91a9351306e975 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Aowen Zhuang Christine Yang Yingying Liu Yanie Tan Simon T. Bond Shannen Walker Tim Sikora Adrienne Laskowski Arpeeta Sharma Judy B. de Haan Peter J. Meikle Takahiko Shimizu Melinda T. Coughlan Anna C. Calkin Brian G. Drew |
spellingShingle |
Aowen Zhuang Christine Yang Yingying Liu Yanie Tan Simon T. Bond Shannen Walker Tim Sikora Adrienne Laskowski Arpeeta Sharma Judy B. de Haan Peter J. Meikle Takahiko Shimizu Melinda T. Coughlan Anna C. Calkin Brian G. Drew SOD2 in skeletal muscle: New insights from an inducible deletion model Redox Biology Skeletal muscle Superoxide ROS Lipid metabolism Mitochondria |
author_facet |
Aowen Zhuang Christine Yang Yingying Liu Yanie Tan Simon T. Bond Shannen Walker Tim Sikora Adrienne Laskowski Arpeeta Sharma Judy B. de Haan Peter J. Meikle Takahiko Shimizu Melinda T. Coughlan Anna C. Calkin Brian G. Drew |
author_sort |
Aowen Zhuang |
title |
SOD2 in skeletal muscle: New insights from an inducible deletion model |
title_short |
SOD2 in skeletal muscle: New insights from an inducible deletion model |
title_full |
SOD2 in skeletal muscle: New insights from an inducible deletion model |
title_fullStr |
SOD2 in skeletal muscle: New insights from an inducible deletion model |
title_full_unstemmed |
SOD2 in skeletal muscle: New insights from an inducible deletion model |
title_sort |
sod2 in skeletal muscle: new insights from an inducible deletion model |
publisher |
Elsevier |
series |
Redox Biology |
issn |
2213-2317 |
publishDate |
2021-11-01 |
description |
Metabolic conditions such as obesity, insulin resistance and glucose intolerance are frequently associated with impairments in skeletal muscle function and metabolism. This is often linked to dysregulation of homeostatic pathways including an increase in reactive oxygen species (ROS) and oxidative stress. One of the main sites of ROS production is the mitochondria, where the flux of substrates through the electron transport chain (ETC) can result in the generation of oxygen free radicals. Fortunately, several mechanisms exist to buffer bursts of intracellular ROS and peroxide production, including the enzymes Catalase, Glutathione Peroxidase and Superoxide Dismutase (SOD). Of the latter, there are two intracellular isoforms; SOD1 which is mostly cytoplasmic, and SOD2 which is found exclusively in the mitochondria. Developmental and chronic loss of these enzymes has been linked to disease in several studies, however the temporal effects of these disturbances remain largely unexplored. Here, we induced a post-developmental (8-week old mice) deletion of SOD2 in skeletal muscle (SOD2-iMKO) and demonstrate that 16 weeks of SOD2 deletion leads to no major impairment in whole body metabolism, despite these mice displaying alterations in aspects of mitochondrial abundance and voluntary ambulatory movement. This is likely partly explained by the suggestive data that a compensatory response may exist from other redox enzymes, including catalase and glutathione peroxidases. Nevertheless, we demonstrated that inducible SOD2 deletion impacts on specific aspects of muscle lipid metabolism, including the abundance of phospholipids and phosphatidic acid (PA), the latter being a key intermediate in several cellular signaling pathways. Thus, our findings suggest that post-developmental deletion of SOD2 induces a more subtle phenotype than previous embryonic models have shown, allowing us to highlight a previously unrecognized link between SOD2, mitochondrial function and bioactive lipid species including PA. |
topic |
Skeletal muscle Superoxide ROS Lipid metabolism Mitochondria |
url |
http://www.sciencedirect.com/science/article/pii/S2213231721002949 |
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doaj-ae96313ccf2649e18f91a9351306e9752021-09-29T04:24:58ZengElsevierRedox Biology2213-23172021-11-0147102135SOD2 in skeletal muscle: New insights from an inducible deletion modelAowen Zhuang0Christine Yang1Yingying Liu2Yanie Tan3Simon T. Bond4Shannen Walker5Tim Sikora6Adrienne Laskowski7Arpeeta Sharma8Judy B. de Haan9Peter J. Meikle10Takahiko Shimizu11Melinda T. Coughlan12Anna C. Calkin13Brian G. Drew14Baker Heart & Diabetes Institute, Melbourne, 3004, Australia; Central Clinical School, Monash University, Melbourne, 3004, Australia; Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, AustraliaBaker Heart & Diabetes Institute, Melbourne, 3004, AustraliaBaker Heart & Diabetes Institute, Melbourne, 3004, AustraliaBaker Heart & Diabetes Institute, Melbourne, 3004, Australia; Central Clinical School, Monash University, Melbourne, 3004, AustraliaBaker Heart & Diabetes Institute, Melbourne, 3004, Australia; Central Clinical School, Monash University, Melbourne, 3004, Australia; Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, AustraliaBaker Heart & Diabetes Institute, Melbourne, 3004, Australia; Central Clinical School, Monash University, Melbourne, 3004, AustraliaBaker Heart & Diabetes Institute, Melbourne, 3004, AustraliaDepartment of Diabetes, Central Clinical School, Monash University, Melbourne, 3004, AustraliaBaker Heart & Diabetes Institute, Melbourne, 3004, AustraliaBaker Heart & Diabetes Institute, Melbourne, 3004, Australia; Central Clinical School, Monash University, Melbourne, 3004, Australia; Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, Australia; Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, 3083, Australia; Faculty of Science, Engineering and Technology, Swinburne University, Melbourne, 3122, AustraliaBaker Heart & Diabetes Institute, Melbourne, 3004, Australia; Central Clinical School, Monash University, Melbourne, 3004, Australia; Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, AustraliaAging Stress Response Research Project Team, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, JapanBaker Heart & Diabetes Institute, Melbourne, 3004, Australia; Department of Diabetes, Central Clinical School, Monash University, Melbourne, 3004, AustraliaBaker Heart & Diabetes Institute, Melbourne, 3004, Australia; Central Clinical School, Monash University, Melbourne, 3004, Australia; Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, AustraliaBaker Heart & Diabetes Institute, Melbourne, 3004, Australia; Central Clinical School, Monash University, Melbourne, 3004, Australia; Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, Australia; Corresponding author. Baker Heart & Diabetes Institute, Melbourne, 3004, Australia.Metabolic conditions such as obesity, insulin resistance and glucose intolerance are frequently associated with impairments in skeletal muscle function and metabolism. This is often linked to dysregulation of homeostatic pathways including an increase in reactive oxygen species (ROS) and oxidative stress. One of the main sites of ROS production is the mitochondria, where the flux of substrates through the electron transport chain (ETC) can result in the generation of oxygen free radicals. Fortunately, several mechanisms exist to buffer bursts of intracellular ROS and peroxide production, including the enzymes Catalase, Glutathione Peroxidase and Superoxide Dismutase (SOD). Of the latter, there are two intracellular isoforms; SOD1 which is mostly cytoplasmic, and SOD2 which is found exclusively in the mitochondria. Developmental and chronic loss of these enzymes has been linked to disease in several studies, however the temporal effects of these disturbances remain largely unexplored. Here, we induced a post-developmental (8-week old mice) deletion of SOD2 in skeletal muscle (SOD2-iMKO) and demonstrate that 16 weeks of SOD2 deletion leads to no major impairment in whole body metabolism, despite these mice displaying alterations in aspects of mitochondrial abundance and voluntary ambulatory movement. This is likely partly explained by the suggestive data that a compensatory response may exist from other redox enzymes, including catalase and glutathione peroxidases. Nevertheless, we demonstrated that inducible SOD2 deletion impacts on specific aspects of muscle lipid metabolism, including the abundance of phospholipids and phosphatidic acid (PA), the latter being a key intermediate in several cellular signaling pathways. Thus, our findings suggest that post-developmental deletion of SOD2 induces a more subtle phenotype than previous embryonic models have shown, allowing us to highlight a previously unrecognized link between SOD2, mitochondrial function and bioactive lipid species including PA.http://www.sciencedirect.com/science/article/pii/S2213231721002949Skeletal muscleSuperoxideROSLipid metabolismMitochondria |