Mff functions with Pex11pβ and DLP1 in peroxisomal fission
Open Access
- 14 August 2013
- journal article
- Published by The Company of Biologists in Biology Open
- Vol. 2 (10), 998-1006
- https://doi.org/10.1242/bio.20135298
Abstract
Summary Peroxisomal division comprises three steps: elongation, constriction, and fission. Translocation of dynamin-like protein 1 (DLP1), a member of the large GTPase family, from the cytosol to peroxisomes is a prerequisite for membrane fission; however, the molecular machinery for peroxisomal targeting of DLP1 remains unclear. This study investigated whether mitochondrial fission factor (Mff), which targets DLP1 to mitochondria, may also recruit DLP1 to peroxisomes. Results show that endogenous Mff is localized to peroxisomes, especially at the membrane-constricted regions of elongated peroxisomes, in addition to mitochondria. Knockdown of MFF abrogates the fission stage of peroxisomal division and is associated with failure to recruit DLP1 to peroxisomes, while ectopic expression of MFF increases the peroxisomal targeting of DLP1. Co-expression of MFF and PEX11β, the latter being a key player in peroxisomal elongation, increases peroxisome abundance. Overexpression of MFF also increases the interaction between DLP1 and Pex11pβ, which knockdown of MFF, but not Fis1, abolishes. Moreover, results show that Pex11pβ interacts with Mff in a DLP1-dependent manner. In conclusion, Mff contributes to the peroxisomal targeting of DLP1 and plays a key role in the fission of the peroxisomal membrane by acting in concert with Pex11pβ and DLP1.This publication has 51 references indexed in Scilit:
- The crystal structure of dynaminNature, 2011
- A Lethal de Novo Mutation in the Middle Domain of the Dynamin-related GTPase Drp1 Impairs Higher Order Assembly and Mitochondrial DivisionOnline Journal of Public Health Informatics, 2010
- Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondriaProceedings of the National Academy of Sciences of the United States of America, 2008
- The Novel Tail-anchored Membrane Protein Mff Controls Mitochondrial and Peroxisomal Fission in Mammalian CellsMolecular Biology of the Cell, 2008
- Clinical, biochemical, and mutational spectrum of peroxisomal acyl–coenzyme A oxidase deficiencyHuman Mutation, 2007
- The WD40 protein Caf4p is a component of the mitochondrial fission machinery and recruits Dnm1p to mitochondriaThe Journal of cell biology, 2005
- Dynamin family of mechanoenzymesCurrent Opinion in Cell Biology, 2001
- cDNA Cloning and Characterization of a Constitutively Expressed Isoform of the Human Peroxin Pex11pBiochemical and Biophysical Research Communications, 1998
- Clofibrate‐inducible, 28‐kDa peroxisomal integral membrane protein is encoded by PEX11FEBS Letters, 1998
- Giant peroxisomes in oleic acid-induced Saccharomyces cerevisiae lacking the peroxisomal membrane protein Pmp27p.The Journal of cell biology, 1995