Limiting Mrs2-dependent mitochondrial Mg2+ uptake induces metabolic programming in prolonged dietary stress
Summary: The most abundant cellular divalent cations, Mg2+ (mM) and Ca2+ (nM-μM), antagonistically regulate divergent metabolic pathways with several orders of magnitude affinity preference, but the physiological significance of this competition remains elusive. In mice consuming a Western diet, gen...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723001663 |
| _version_ | 1811162722909290496 |
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| author | Travis R. Madaris Manigandan Venkatesan Soumya Maity Miriam C. Stein Neelanjan Vishnu Mridula K. Venkateswaran James G. Davis Karthik Ramachandran Sukanthathulse Uthayabalan Cristel Allen Ayodeji Osidele Kristen Stanley Nicholas P. Bigham Terry M. Bakewell Melanie Narkunan Amy Le Varsha Karanam Kang Li Aum Mhapankar Luke Norton Jean Ross M. Imran Aslam W. Brian Reeves Brij B. Singh Jeffrey Caplan Justin J. Wilson Peter B. Stathopulos Joseph A. Baur Muniswamy Madesh |
| author_facet | Travis R. Madaris Manigandan Venkatesan Soumya Maity Miriam C. Stein Neelanjan Vishnu Mridula K. Venkateswaran James G. Davis Karthik Ramachandran Sukanthathulse Uthayabalan Cristel Allen Ayodeji Osidele Kristen Stanley Nicholas P. Bigham Terry M. Bakewell Melanie Narkunan Amy Le Varsha Karanam Kang Li Aum Mhapankar Luke Norton Jean Ross M. Imran Aslam W. Brian Reeves Brij B. Singh Jeffrey Caplan Justin J. Wilson Peter B. Stathopulos Joseph A. Baur Muniswamy Madesh |
| author_sort | Travis R. Madaris |
| collection | DOAJ |
| description | Summary: The most abundant cellular divalent cations, Mg2+ (mM) and Ca2+ (nM-μM), antagonistically regulate divergent metabolic pathways with several orders of magnitude affinity preference, but the physiological significance of this competition remains elusive. In mice consuming a Western diet, genetic ablation of the mitochondrial Mg2+ channel Mrs2 prevents weight gain, enhances mitochondrial activity, decreases fat accumulation in the liver, and causes prominent browning of white adipose. Mrs2 deficiency restrains citrate efflux from the mitochondria, making it unavailable to support de novo lipogenesis. As citrate is an endogenous Mg2+ chelator, this may represent an adaptive response to a perceived deficit of the cation. Transcriptional profiling of liver and white adipose reveals higher expression of genes involved in glycolysis, β-oxidation, thermogenesis, and HIF-1α-targets, in Mrs2−/− mice that are further enhanced under Western-diet-associated metabolic stress. Thus, lowering mMg2+ promotes metabolism and dampens diet-induced obesity and metabolic syndrome. |
| first_indexed | 2024-04-10T06:33:48Z |
| format | Article |
| id | doaj.art-324fd2ad3fb9463fa4701a04cb364947 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-10T06:33:48Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-324fd2ad3fb9463fa4701a04cb3649472023-03-01T04:31:31ZengElsevierCell Reports2211-12472023-03-01423112155Limiting Mrs2-dependent mitochondrial Mg2+ uptake induces metabolic programming in prolonged dietary stressTravis R. Madaris0Manigandan Venkatesan1Soumya Maity2Miriam C. Stein3Neelanjan Vishnu4Mridula K. Venkateswaran5James G. Davis6Karthik Ramachandran7Sukanthathulse Uthayabalan8Cristel Allen9Ayodeji Osidele10Kristen Stanley11Nicholas P. Bigham12Terry M. Bakewell13Melanie Narkunan14Amy Le15Varsha Karanam16Kang Li17Aum Mhapankar18Luke Norton19Jean Ross20M. Imran Aslam21W. Brian Reeves22Brij B. Singh23Jeffrey Caplan24Justin J. Wilson25Peter B. Stathopulos26Joseph A. Baur27Muniswamy Madesh28Department of Medicine, Center for Mitochondrial Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Department of Medicine, Cardiology/Diabetes Divisions, University of Texas Health San Antonio, San Antonio, TX 78229, USADepartment of Medicine, Center for Mitochondrial Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Department of Medicine, Cardiology/Diabetes Divisions, University of Texas Health San Antonio, San Antonio, TX 78229, USADepartment of Medicine, Center for Mitochondrial Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Department of Medicine, Cardiology/Diabetes Divisions, University of Texas Health San Antonio, San Antonio, TX 78229, USADepartment of Medicine, Center for Mitochondrial Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Department of Medicine, Cardiology/Diabetes Divisions, University of Texas Health San Antonio, San Antonio, TX 78229, USADepartment of Medicine, Center for Mitochondrial Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Department of Medicine, Cardiology/Diabetes Divisions, University of Texas Health San Antonio, San Antonio, TX 78229, USADepartment of Medicine, Center for Mitochondrial Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Department of Medicine, Cardiology/Diabetes Divisions, University of Texas Health San Antonio, San Antonio, TX 78229, USADepartment of Physiology and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA 19103, USADepartment of Medicine, Center for Mitochondrial Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Department of Medicine, Cardiology/Diabetes Divisions, University of Texas Health San Antonio, San Antonio, TX 78229, USADepartment of Physiology and Pharmacology, Western University, London, ON N6A 5C1, CanadaDepartment of Medicine, Center for Mitochondrial Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Department of Medicine, Cardiology/Diabetes Divisions, University of Texas Health San Antonio, San Antonio, TX 78229, USADepartment of Medicine, Center for Mitochondrial Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Department of Medicine, Cardiology/Diabetes Divisions, University of Texas Health San Antonio, San Antonio, TX 78229, USADepartment of Medicine, Center for Mitochondrial Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Department of Medicine, Cardiology/Diabetes Divisions, University of Texas Health San Antonio, San Antonio, TX 78229, USADepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USADepartment of Medicine, Cardiology/Diabetes Divisions, University of Texas Health San Antonio, San Antonio, TX 78229, USADepartment of Medicine, Center for Mitochondrial Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Department of Medicine, Cardiology/Diabetes Divisions, University of Texas Health San Antonio, San Antonio, TX 78229, USADepartment of Medicine, Center for Mitochondrial Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Department of Medicine, Cardiology/Diabetes Divisions, University of Texas Health San Antonio, San Antonio, TX 78229, USADepartment of Medicine, Center for Mitochondrial Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Department of Medicine, Cardiology/Diabetes Divisions, University of Texas Health San Antonio, San Antonio, TX 78229, USADepartment of Medicine, Center for Mitochondrial Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Department of Medicine, Cardiology/Diabetes Divisions, University of Texas Health San Antonio, San Antonio, TX 78229, USADepartment of Medicine, Center for Mitochondrial Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Department of Medicine, Cardiology/Diabetes Divisions, University of Texas Health San Antonio, San Antonio, TX 78229, USADepartment of Medicine, Cardiology/Diabetes Divisions, University of Texas Health San Antonio, San Antonio, TX 78229, USADepartment of Biological Sciences, Delaware Biotechnology Institute, University of Delaware, Newark, DE 19711, USADepartment of Medicine, Cardiology/Diabetes Divisions, University of Texas Health San Antonio, San Antonio, TX 78229, USADepartment of Medicine, Center for Mitochondrial Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Department of Medicine, Cardiology/Diabetes Divisions, University of Texas Health San Antonio, San Antonio, TX 78229, USADepartment of Medicine, Center for Mitochondrial Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USADepartment of Biological Sciences, Delaware Biotechnology Institute, University of Delaware, Newark, DE 19711, USADepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USADepartment of Physiology and Pharmacology, Western University, London, ON N6A 5C1, CanadaDepartment of Physiology and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA 19103, USA; Corresponding authorDepartment of Medicine, Center for Mitochondrial Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Department of Medicine, Cardiology/Diabetes Divisions, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Corresponding authorSummary: The most abundant cellular divalent cations, Mg2+ (mM) and Ca2+ (nM-μM), antagonistically regulate divergent metabolic pathways with several orders of magnitude affinity preference, but the physiological significance of this competition remains elusive. In mice consuming a Western diet, genetic ablation of the mitochondrial Mg2+ channel Mrs2 prevents weight gain, enhances mitochondrial activity, decreases fat accumulation in the liver, and causes prominent browning of white adipose. Mrs2 deficiency restrains citrate efflux from the mitochondria, making it unavailable to support de novo lipogenesis. As citrate is an endogenous Mg2+ chelator, this may represent an adaptive response to a perceived deficit of the cation. Transcriptional profiling of liver and white adipose reveals higher expression of genes involved in glycolysis, β-oxidation, thermogenesis, and HIF-1α-targets, in Mrs2−/− mice that are further enhanced under Western-diet-associated metabolic stress. Thus, lowering mMg2+ promotes metabolism and dampens diet-induced obesity and metabolic syndrome.http://www.sciencedirect.com/science/article/pii/S2211124723001663CP: Metabolism |
| spellingShingle | Travis R. Madaris Manigandan Venkatesan Soumya Maity Miriam C. Stein Neelanjan Vishnu Mridula K. Venkateswaran James G. Davis Karthik Ramachandran Sukanthathulse Uthayabalan Cristel Allen Ayodeji Osidele Kristen Stanley Nicholas P. Bigham Terry M. Bakewell Melanie Narkunan Amy Le Varsha Karanam Kang Li Aum Mhapankar Luke Norton Jean Ross M. Imran Aslam W. Brian Reeves Brij B. Singh Jeffrey Caplan Justin J. Wilson Peter B. Stathopulos Joseph A. Baur Muniswamy Madesh Limiting Mrs2-dependent mitochondrial Mg2+ uptake induces metabolic programming in prolonged dietary stress Cell Reports CP: Metabolism |
| title | Limiting Mrs2-dependent mitochondrial Mg2+ uptake induces metabolic programming in prolonged dietary stress |
| title_full | Limiting Mrs2-dependent mitochondrial Mg2+ uptake induces metabolic programming in prolonged dietary stress |
| title_fullStr | Limiting Mrs2-dependent mitochondrial Mg2+ uptake induces metabolic programming in prolonged dietary stress |
| title_full_unstemmed | Limiting Mrs2-dependent mitochondrial Mg2+ uptake induces metabolic programming in prolonged dietary stress |
| title_short | Limiting Mrs2-dependent mitochondrial Mg2+ uptake induces metabolic programming in prolonged dietary stress |
| title_sort | limiting mrs2 dependent mitochondrial mg2 uptake induces metabolic programming in prolonged dietary stress |
| topic | CP: Metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723001663 |
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