ArticleProceedings of the National Academy of Sciences of the United States of America2020
An essential role for cardiolipin in the stability and function of the mitochondrial calcium uniporter.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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57 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.
- Knowledge mapping of mitochondrial calcium uniporter from 2011 to 2022: A bibliometric analysis.Frontiers in physiology · 2023Pooled it
- Peroxisomal catalase and plasmalogen biosynthesis protect from oxidative stress in Barth syndrome cardiomyopathy.Basic research in cardiology · 2026Article
- Mitochondrial CaCommunications biology · 2026Article
- Elevating levels of neuronal MCU in the hippocampus enhances mitochondrial calcium uptake and respiratory efficiency proportional to demand.bioRxiv : the preprint server for biology · 2026Article
- Insights into Neutrophil Dysfunction in Inherited Metabolic Disorders.Journal of innate immunity · 2026Review
- Lipidomics Techniques Revealed the Adipogenic Differentiation Mechanism of Bovine Adipose-Derived Neural Crest Stem Cells.Animals : an open access journal from MDPI · 2025Article
- 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
- Structure of MICU from non-metazoan Dictyostelium discoideum reveals unique characteristics.Communications biology · 2025Article
- Barth Syndrome:Genes · 2025Review
- Proteolytic regulation of mitochondrial magnesium channel by m-AAA protease and prohibitin complex.Genetics · 2025Article
- Fasting the mitochondria to prevent neurodegeneration: the role of ceramides.Frontiers in neuroscience · 2025Review
- Aging and Alzheimer's: the critical role of mitochondrial dysfunction and synaptic alterations.Frontiers in synaptic neuroscience · 2025Review
- Systematic mapping of mitochondrial calcium uniporter channel (MCUC)-mediated calcium signaling networks.The EMBO journal · 2024Article
- Simulating Bacterial Membrane Models at the Atomistic Level: A Force Field Comparison.Journal of chemical theory and computation · 2024Article
- Mitochondrial Calcium Regulation of Cardiac Metabolism in Health and Disease.Physiology (Bethesda, Md.) · 2024Review
- Mitochondrial calcium uniporter channel gatekeeping in cardiovascular disease.Nature cardiovascular research · 2024Review
- Depth of Interbreed Difference in Postmortem Bovine Muscle Determined by CE-FT/MS and LC-FT/MS Metabolomics.Metabolites · 2024Article
- Dysregulation of cellular membrane homeostasis as a crucial modulator of cancer risk.The FEBS journal · 2024Review
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7 authors at 3 institutions in 1 country.
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Abstract
Calcium uptake by the mitochondrial calcium uniporter coordinates cytosolic signaling events with mitochondrial bioenergetics. During the past decade all protein components of the mitochondrial calcium uniporter have been identified, including MCU, the pore-forming subunit. However, the specific lipid requirements, if any, for the function and formation of this channel complex are currently not known. Here we utilize yeast, which lacks the mitochondrial calcium uniporter, as a model system to address this problem. We use heterologous expression to functionally reconstitute human uniporter machinery both in wild-type yeast as well as in mutants defective in the biosynthesis of phosphatidylethanolamine, phosphatidylcholine, or cardiolipin (CL). We uncover a specific requirement of CL for in vivo reconstituted MCU stability and activity. The CL requirement of MCU is evolutionarily conserved with loss of CL triggering rapid turnover of MCU homologs and impaired calcium transport. Furthermore, we observe reduced abundance and activity of endogenous MCU in mammalian cellular models of Barth syndrome, which is characterized by a partial loss of CL. MCU abundance is also decreased in the cardiac tissue of Barth syndrome patients. Our work raises the hypothesis that impaired mitochondrial calcium transport contributes to the pathogenesis of Barth syndrome, and more generally, showcases the utility of yeast phospholipid mutants in dissecting the phospholipid requirements of ion channel complexes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.