The Mechanism of Ca2+-Dependent Regulation of Kinesin-Mediated Mitochondrial Motility
Open accessAbstract
Mitochondria are mobile organelles and cells regulate mitochondrial movement in order to meet the changing energy needs of each cellular region. Ca(2+) signaling, which halts both anterograde and retrograde mitochondrial motion, serves as one regulatory input. Anterograde mitochondrial movement is generated by kinesin-1, which interacts with the mitochondrial protein Miro through an adaptor protein, milton. We show that kinesin is present on all axonal mitochondria, including those that are stationary or moving retrograde. We also show that the EF-hand motifs of Miro mediate Ca(2+)-dependent arrest of mitochondria and elucidate the regulatory mechanism. Rather than dissociating kinesin-1 from mitochondria, Ca(2+)-binding permits Miro to interact directly with the motor domain of kinesin-1, preventing motor/microtubule interactions. Thus, kinesin-1 switches from an active state in which it is bound to Miro only via milton, to an inactive state in which direct binding to Miro prevents its interaction with microtubules. Disrupting Ca(2+)-dependent regulation diminishes neuronal resistance to excitotoxicity.
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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 [49]
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“Moreover, it has been largely described that Ca 2+ is a key regulator of mitochondria motility and docking 44 – 49 , 107 .”
- Authors
- Wang, X., & Schwarz, T. L.
- Affiliations
- Boston Children's Hospital (US)
- Corresponding author
- Schwarz, Thomas L.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 136
- Issue
- 1
- Pages
- 163-174
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC2768392
- OpenAlex
- W1996764498
- Cited by
- 871
- References
- 3
- Citations by year
- 2026: 30 · 2025: 44 · 2024: 38 · 2023: 38 · 2022: 38 · 2021: 68 · 2020: 54 · 2019: 58 · 2018: 52 · 2017: 54 · 2016: 56 · 2015: 45 · 2014: 57 · 2013: 55 · 2012: 64
- FWCI
- 24.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1689 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM069808)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- mitochondrial motility, kinesin-1, Miro, John Milton, calcium signaling, EF-hand motifs, Ca2+ binding, axonal mitochondria, excitotoxicity
- MeSH terms
- Animals, Calcium, Cell Line, Cells, Cultured, Hippocampus, Humans, Microtubules, Mitochondria, Nerve Tissue Proteins, Neurons, Kinesins, Mitochondrial Proteins, Rats
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