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The roles of mitochondria in global and local intracellular calcium signalling
Abstract
Activation of Ca 2+ channels in Ca 2+ stores in organelles and the plasma membrane generates cytoplasmic calcium ([Ca 2+]c) signals that control almost every aspect of cell function, including metabolism, vesicle fusion and contraction. Mitochondria have a high capacity for Ca 2+ uptake and chelation, alongside efficient Ca 2+ release mechanisms. Still, mitochondria do not store Ca 2+ in a prolonged manner under physiological conditions and lack the capacity to generate global [Ca 2+]c signals. However, mitochondria take up Ca 2+ at high local [Ca 2+]c signals that originate from neighbouring organelles, and also during sustained global elevations of [Ca 2+]c. Accumulated Ca 2+ in the mitochondria stimulates oxidative metabolism and upon return to the cytoplasm, can produce spatially confined rises in [Ca 2+]c to exert control over processes that are sensitive to Ca 2+. Thus, the mitochondrial handling of [Ca 2+]c is of physiological relevance. Furthermore, dysregulation of mitochondrial Ca 2+ handling can contribute to debilitating diseases. We discuss the mechanisms and relevance of mitochondria in local and global calcium signals.
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“Mitochondria, as critical regulators of intracellular Ca2+ concentration, maintain Ca2+ homeostasis through the absorption and release of Ca2+.”
From Matrix mechanical remodeled carrier-free nanosystem for programmable closed-loop reversal of liver fibrosis via STING alkylation (2025) · cites this paper as [16]
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Mitochondrial dysfunction in energy metabolism: Unraveling cardiometabolic diseases
Gao, J., & Yao, M. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-34186-1.00011-6
Ye, Q., Wu, A., Carillo, K. J., Boyenle, I. D., Hemesath, H. R., He, Y., Delaeter, N., Jeon, J., Orban, J. P., Zhang, L., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.07.29.741579
Jang, D. C., Kim, S. Y., Kim, W. S., Choi, I. Y., Jang, E., Jung, H., Chung, C., Bang, S., Kim, H. N., Choi, H. W., et al. (2026) · Experimental & Molecular Medicine · doi:10.1038/s12276-026-01803-2 · Cited by 3
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Lu, G., Chengxiao, H., Rui, C., Yanrong, G., Ma, S., & Rili, G. (2026) · Scientific Reports · doi:10.1038/s41598-026-56389-6
Cao, N., Zhao, H., Wu, Z., Li, S., Tong, W., Jin, L., Wu, M., Liu, J., Liu, A., Wang, M., et al. (2026) · Redox Biology · doi:10.1016/j.redox.2026.104360
Kawasumi, M., & Teranishi, M. (2026) · Antioxidants · doi:10.3390/antiox15081043
Metadata
- Authors
- Cartes-Saavedra, B., Ghosh, A., & Hajnóczky, G.
- Affiliations
- Thomas Jefferson University (US)
- Corresponding author
- Hajnóczky, György
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2025-01-27
- Volume
- 26
- Issue
- 6
- Pages
- 456-475
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- OpenAlex
- W4406871717
- Cited by
- 126
- References
- 314
- Citations by year
- 2026: 87 · 2025: 38
- FWCI
- 11.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (R03TR004644)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK125897)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- mitochondria, intracellular calcium signaling, mitochondrial calcium uptake, mitochondrial calcium release, intracellular calcium stores, calcium channels, intracellular calcium, oxidative metabolism, disease
- MeSH terms
- Animals, Calcium, Cytoplasm, Humans, Mitochondria, Calcium Channels, Calcium Signaling
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