ArticleHuman molecular genetics2022
MCU-complex-mediated mitochondrial calcium signaling is impaired in Barth syndrome.
Article in Human molecular genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Mechano-energetic uncoupling in heart failure.Nature reviews. Cardiology · 2025Review
- Mitochondrial dysfunction and lipid dysregulation in yeast lacking phosphatidylserine.Molecular biology of the cell · 2025Article
- Mitochondria-Homing Drug Mitochonic Acid 5 Improves Barth Syndrome Myopathy in a Human-Induced Pluripotent Stem Cell Model and Barth Syndrome Drosophila Model.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- The roles of mitochondria in global and local intracellular calcium signalling.Nature reviews. Molecular cell biology · 2025Review
- Mitochondrial calcium signaling regulates branched-chain amino acid catabolism in fibrolamellar carcinoma.Science advances · 2025Article
- Barth Syndrome:Genes · 2025Review
- Proteolytic regulation of mitochondrial magnesium channel by m-AAA protease and prohibitin complex.Genetics · 2025Article
- Mitochondrial Calcium Regulation of Cardiac Metabolism in Health and Disease.Physiology (Bethesda, Md.) · 2024Review
- Upregulation of the AMPK-FOXO1-PDK4 pathway is a primary mechanism of pyruvate dehydrogenase activity reduction in tafazzin-deficient cells.Scientific reports · 2024Article
- Review
- Mitochondrial phospholipid metabolism in health and disease.Journal of cell science · 2023Article
- The Mitochondrial Calcium Uniporter (MCU): Molecular Identity and Role in Human Diseases.Biomolecules · 2023Review
- [Decreased Expression of Mitochondrial Calcium Uptake Protein 1 Leads to Skeletal Muscle Dysfunction in Septic Mice].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2023Article
- Barth Syndrome Cardiomyopathy: An Update.Genes · 2022Review
- Mitochondria in Pathological Cardiac Remodeling.Current opinion in physiology · 2022Article
- Myocardial disturbances of intermediary metabolism in Barth syndrome.Frontiers in cardiovascular medicine · 2022Review
- Studying Lipid-Related Pathophysiology Using the Yeast Model.Frontiers in physiology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Calcium signaling via mitochondrial calcium uniporter (MCU) complex coordinates mitochondrial bioenergetics with cellular energy demands. Emerging studies show that the stability and activity of the pore-forming subunit of the complex, MCU, is dependent on the mitochondrial phospholipid, cardiolipin (CL), but how this impacts calcium-dependent mitochondrial bioenergetics in CL-deficiency disorder like Barth syndrome (BTHS) is not known. Here we utilized multiple models of BTHS including yeast, mouse muscle cell line, as well as BTHS patient cells and cardiac tissue to show that CL is required for the abundance and stability of the MCU-complex regulatory subunit MICU1. Interestingly, the reduction in MICU1 abundance in BTHS mitochondria is independent of MCU. Unlike MCU and MICU1/MICU2, other subunit and associated factor of the uniporter complex, EMRE and MCUR1, respectively, are not affected in BTHS models. Consistent with the decrease in MICU1 levels, we show that the kinetics of MICU1-dependent mitochondrial calcium uptake is perturbed and acute stimulation of mitochondrial calcium signaling in BTHS myoblasts fails to activate pyruvate dehydrogenase, which in turn impairs the generation of reducing equivalents and blunts mitochondrial bioenergetics. Taken together, our findings suggest that defects in mitochondrial calcium signaling could contribute to cardiac and skeletal muscle pathologies observed in BTHS patients.
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