Cited by 1,110Mitochondrial Function and PathologyAutophagy in Disease and TherapyCell death mechanisms and regulation

Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells

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Otera, Hidenori, Wang, Chunxin, Cleland, Megan M., Setoguchi, Kiyoko, Yokota, Sadaki, Youle, Richard J., Mihara, Katsuyoshi·2010·Journal of Cell Biology

Abstract

The cytoplasmic dynamin-related guanosine triphosphatase Drp1 is recruited to mitochondria and mediates mitochondrial fission. Although the mitochondrial outer membrane (MOM) protein Fis1 is thought to be a Drp1 receptor, this has not been confirmed. To analyze the mechanism of Drp1 recruitment, we manipulated the expression of mitochondrial fission and fusion proteins and demonstrated that (a) mitochondrial fission factor (Mff) knockdown released the Drp1 foci from the MOM accompanied by network extension, whereas Mff overexpression stimulated mitochondrial recruitment of Drp1 accompanied by mitochondrial fission; (b) Mff-dependent mitochondrial fission proceeded independent of Fis1; (c) a Mff mutant with the plasma membrane–targeted CAAX motif directed Drp1 to the target membrane; (d) Mff and Drp1 physically interacted in vitro and in vivo; (e) exogenous stimuli–induced mitochondrial fission and apoptosis were compromised by knockdown of Drp1 and Mff but not Fis1; and (f) conditional knockout of Fis1 in colon carcinoma cells revealed that it is dispensable for mitochondrial fission. Thus, Mff functions as an essential factor in mitochondrial recruitment of Drp1.

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Authors
Otera, H., Wang, C., Cleland, M. M., Setoguchi, K., Yokota, S., Youle, R. J., & Mihara, K.
Affiliations
  • Kyushu University (JP)
  • National Institutes of Health (US)
  • Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892 2
  • Nagasaki International University (JP)
Corresponding author
Mihara, Katsuyoshi
Venue
Journal of Cell Biology
Published
2010-12-13
Volume
191
Issue
6
Pages
1141-1158
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
OpenAlex
W2149108521
Cited by
1,110
References
62
Citations by year
2026: 42 · 2025: 67 · 2024: 74 · 2023: 72 · 2022: 88 · 2021: 91 · 2020: 80 · 2019: 69 · 2018: 70 · 2017: 70 · 2016: 77 · 2015: 71 · 2014: 78 · 2013: 60 · 2012: 67
FWCI
20.43
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
National Institutes of Health
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 › Molecular Biology › Cell death mechanisms and regulation
Keywords
Mff, Drp1, mitochondrial fission, mitochondrial recruitment, Fis1, mitochondrial outer membrane, dynamin-related GTPase, mitochondrial fusion, CAAX motif, apoptosis, colon cancer cells, conditional knockout
MeSH terms
Animals, Cells, Cultured, Cytoplasm, Cytoskeletal Proteins, HeLa Cells, Humans, Membrane Proteins, Mitochondria, Down-Regulation, GTP Phosphohydrolases, Mitochondrial Proteins, RNA, Small Interfering

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