Bidirectional Ca 2+ -dependent control of mitochondrial dynamics by the Miro GTPase
Open accessAbstract
Calcium oscillations suppress mitochondrial movements along the microtubules to support on-demand distribution of mitochondria. To activate this mechanism, Ca 2+ targets a yet unidentified cytoplasmic factor that does not seem to be a microtubular motor or a kinase/phosphatase. Here, we have studied the dependence of mitochondrial dynamics on the Miro GTPases that reside in the mitochondria and contain two EF-hand Ca 2+ -binding domains, in H9c2 cells and primary neurons. At resting cytoplasmic [Ca 2+ ] ([Ca 2+ ] c ), movements of the mitochondria were enhanced by Miro overexpression irrespective of the presence of the EF-hands. The Ca 2+ -induced arrest of mitochondrial motility was also promoted by Miro overexpression and was suppressed when either the Miro were depleted or their EF-hand was mutated. Miro also enhanced the fusion state of the mitochondria at resting [Ca 2+ ] c but promoted mitochondrial fragmentation at high [Ca 2+ ] c . These effects of Miro on mitochondrial morphology seem to involve Drp1 suppression and activation, respectively. In primary neurons, Miro also caused an increase in dendritic mitochondrial mass and enhanced mitochondrial calcium signaling. Thus, Miro proteins serve as a [Ca 2+ ] c -sensitive switch and bifunctional regulator for both the motility and fusion-fission dynamics of the mitochondria.
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Ca2+ is a key regulator of mitochondria motility and docking.
“it has been largely described that Ca2+ is a key regulator of mitochondria motility and docking44–49,107.”
From CYFIP1 governs the development of cortical axons by modulating calcium availability (2025) · cites this paper as [47]
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- Authors
- Saotome, M., Safiulina, D., Szabadkai, G., Das, S., Fransson, Å., Aspenstrom, P., Rizzuto, R., & Hajnóczky, G.
- Affiliations
- Thomas Jefferson University (US)
- University of Ferrara (IT)
- Uppsala University (SE)
- Ludwig Institute for Cancer Research, Biomedical Center, Uppsala University, SE-751 24 Uppsala, Sweden
- Corresponding author
- Hajnóczky, György
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-12-30
- Volume
- 105
- Issue
- 52
- Pages
- 20728-20733
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2634948
- OpenAlex
- W2095652212
- Cited by
- 538
- References
- 1
- Citations by year
- 2026: 21 · 2025: 23 · 2024: 31 · 2023: 25 · 2022: 29 · 2021: 34 · 2020: 30 · 2019: 36 · 2018: 37 · 2017: 44 · 2016: 30 · 2015: 24 · 2014: 31 · 2013: 29 · 2012: 34
- FWCI
- 10.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- Eesti Teadusfondi
- Cancerfonden
- Vetenskapsrådet
- Associazione Italiana per la Ricerca sul Cancro (1P01AG025532-01A1)
- Università degli Studi di Ferrara
- National Institutes of Health
- National Institute on Aging (P01AG025532)
- National Institute of General Medical Sciences (GM 59419, R01GM059419)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-51526, R29DK051526, R01DK051526)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- mitochondrial dynamics, mitochondrial motility, calcium signaling, EF-hand calcium-binding domain, mitochondrial fusion, mitochondrial fission, Drp1, mitochondrial calcium signaling, dendritic mitochondria, neurons, H9c2 cells
- MeSH terms
- Animals, Biological Clocks, Calcium, Cell Line, Dendrites, Humans, Mitochondria, Nerve Tissue Proteins, Rats, Wistar, Protein Structure, Tertiary, Calcium Signaling, rho GTP-Binding Proteins, Mitochondrial Proteins, Dynamins, Rats
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