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PMID: 21149567 Published · ppublish English Journal Article Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

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

The Journal of cell biology ·Vol. 191 ·No. 6 ·2010-12-13 ·Pages 1141-58

Otera H, Wang C, Cleland MM, Setoguchi K, Yokota S, Youle RJ, Mihara K

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.

MeSH Terms
Animals Cells, Cultured Cytoplasm/metabolism Cytoskeletal Proteins/genetics,metabolism Down-Regulation GTP Phosphohydrolases/metabolism HeLa Cells Humans Membrane Proteins/genetics,metabolism,physiology Mitochondria/metabolism Mitochondrial Proteins/genetics,metabolism,physiology RNA, Small Interfering/metabolism
Chemicals
Cytoskeletal Proteins FIS1 protein, human Membrane Proteins Mff protein, human Mitochondrial Proteins RNA, Small Interfering GTP Phosphohydrolases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Otera Hidenori
Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan.
Wang Chunxin
Cleland Megan M
Setoguchi Kiyoko
Yokota Sadaki
Youle Richard J
Mihara Katsuyoshi
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.201007152
Published
2010-12-13
Pages
1141-58
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC3002033
Subset
IM
Grants
Intramural NIH HHS · United States
External Links
PubMed source DOI: 10.1083/jcb.201007152 PMC Full Text View journal details
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