Regulation of mitochondrial Ca2+ and its effects on energetics and redox balance in normal and failing heart
Open accessAbstract
Ca(2+) has been well accepted as a signal that coordinates changes in cytosolic workload with mitochondrial energy metabolism in cardiomyocytes. During increased work, Ca(2+) is accumulated in mitochondria and stimulates ATP production to match energy supply and demand. The kinetics of mitochondrial Ca(2+) ([Ca(2+)](m)) uptake remains unclear, and we review the debate on this subject in this article. [Ca(2+)](m) has multiple targets in oxidative phosphorylation including the F1/FO ATPase, the adenine nucleotide translocase, and Ca(2+)-sensitive dehydrogenases (CaDH) of the tricarboxylic acid (TCA) cycle. The well established effect of [Ca(2+)](m) is to activate CaDHs of the TCA cycle to increase NADH production. Maintaining NADH level is not only critical to keep a high oxidative phosphorylation rate during increased cardiac work, but is also necessary for the reducing system of the cell to maintain its reactive oxygen species (ROS) -scavenging capacity. Further, we review recent data demonstrating the deleterious effects of elevated Na(+) in cardiac pathology by blunting [Ca(2+)](m) accumulation.
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Mitochondrial uptake of Ca2+ is regulated in part by release of intracellular stores from compartments such as the endoplasmic reticulum or sarcoplasmic reticulum in muscle cells.
“Mitochondrial uptake of Ca2+ is regulated, in part, by the release of intracellular stores from compartments such as the endoplasmic reticulum or the sarcoplasmic reticulum in muscle cells (261, 352).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [261]
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- Authors
- Liu, T., & O’Rourke, B.
- Affiliations
- Johns Hopkins University (US)
- ORCID
- Liu, Ting
- Venue
- Journal of Bioenergetics and Biomembranes
- Published
- 2009-04
- Volume
- 41
- Issue
- 2
- Pages
- 127-132
- ISSN
- 0145-479X (ISSN-L)
- 1573-6881
- PMC
- PMC2946065
- OpenAlex
- W1984661543
- Cited by
- 102
- References
- 61
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 2 · 2020: 7 · 2019: 6 · 2018: 4 · 2017: 5 · 2016: 6 · 2015: 4 · 2014: 8 · 2013: 9 · 2012: 16
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Bioenergetics and Biomembranes (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (P01HL081427, R01HL101235)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- mitochondrial calcium, myocardial energy metabolism, oxidative phosphorylation, adenine nucleotide translocase, TCA cycle, NADH production, redox homeostasis, reactive oxygen species scavenging, heart failure, sodium accumulation, cardiomyocytes
- MeSH terms
- Mitochondrial ADP, ATP Translocases, Adenosine Triphosphate, Animals, Calcium, Citric Acid Cycle, Proton-Translocating ATPases, Heart Failure, Humans, Mitochondria, Heart, Myocardium, NAD, Oxidation-Reduction, Oxidative Phosphorylation, Sodium, Reactive Oxygen Species
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