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Cited by 380Mitochondrial Function and PathologyAutophagy in Disease and TherapyMicrotubule and mitosis dynamics

RALA and RALBP1 regulate mitochondrial fission at mitosis

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Kashatus, David F., Lim, Kian-Huat, Brady, Donita C., Pershing, Nicole L. K., Cox, Adrienne D., Counter, Christopher M.·2011·Nature Cell Biology
DOI 10.1038/ncb2310PMC PMC3167028
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Abstract

Mitochondria exist as dynamic interconnected networks that are maintained through a balance of fusion and fission. Equal distribution of mitochondria to daughter cells during mitosis requires fission. Mitotic mitochondrial fission depends on both the relocalization of the large GTPase DRP1 to the outer mitochondrial membrane and phosphorylation of Ser 616 on DRP1 by the mitotic kinase cyclin B-CDK1 (ref. 2). We now report that these processes are mediated by the small Ras-like GTPase RALA and its effector RALBP1 (also known as RLIP76, RLIP1 or RIP1; refs 3, 4). Specifically, the mitotic kinase Aurora A phosphorylates Ser 194 of RALA, relocalizing it to the mitochondria, where it concentrates RALBP1 and DRP1. Furthermore, RALBP1 is associated with cyclin B-CDK1 kinase activity that leads to phosphorylation of DRP1 on Ser 616. Disrupting either RALA or RALBP1 leads to a loss of mitochondrial fission at mitosis, improper segregation of mitochondria during cytokinesis and a decrease in ATP levels and cell number. Thus, the two mitotic kinases Aurora A and cyclin B-CDK1 converge on RALA and RALBP1 to promote mitochondrial fission, the appropriate distribution of mitochondria to daughter cells and ultimately proper mitochondrial function.

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Authors
Kashatus, D. F., Lim, K.-H., Brady, D. C., Pershing, N. L. K., Cox, A. D., & Counter, C. M.
Affiliations
  • Duke Medical Center (US)
  • National Institutes of Health (US)
  • University of North Carolina at Chapel Hill (US)
  • Duke University (US)
Corresponding author
Counter, Christopher M.
ORCID
Venue
Nature Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2011-08-07
Volume
13
Issue
9
Pages
1108-1115
ISSN
  • 1465-7392 (ISSN-L)
  • 1476-4679
DOI
10.1038/ncb2310
PMC
PMC3167028
OpenAlex
W2068876164
Cited by
380
References
4
Citations by year
2026: 13 · 2025: 17 · 2024: 33 · 2023: 25 · 2022: 20 · 2021: 34 · 2020: 30 · 2019: 24 · 2018: 17 · 2017: 21 · 2016: 36 · 2015: 26 · 2014: 29 · 2013: 25 · 2012: 23
FWCI
10.11
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • UNC Libraries
Funders
  • Leukemia and Lymphoma Society
  • National Institutes of Health
  • National Cancer Institute (CA94184, R01CA094184)
  • National Institute of General Medical Sciences (T32GM007171)
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 › Cell Biology › Microtubule and mitosis dynamics
Keywords
mitochondrial fission, mitosis, RalA, RALBP1, Drp1, AURKA, CDK1/cyclin B, mitochondrial segregation, cytokinesis, Ras-related GTPases, mitochondrial distribution, ATP levels, mitochondrial function
MeSH terms
Adenosine Triphosphate, Cell Line, HeLa Cells, Humans, Luminescent Proteins, Microscopy, Fluorescence, Microtubule-Associated Proteins, Mitochondria, Mitosis, Models, Biological, Phosphorylation, Protein Binding, Serine, Immunoblotting, CDC2 Protein Kinase, Protein Serine-Threonine Kinases, ATP-Binding Cassette Transporters, Microscopy, Confocal, Cyclin B, GTP Phosphohydrolases, GTPase-Activating Proteins, ral GTP-Binding Proteins, Mitochondrial Proteins, Dynamins, RNA Interference, Cell Proliferation, Aurora Kinases

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