Mff functions with Pex11pβ and DLP1 in peroxisomal fission

Abstract

SummaryPeroxisomal 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.

The membrane remodeling protein Pex11p activates the GTPase Dnm1p during peroxisomal fission

“…Previous data from mammalian cells suggested that Pex11β binds indirectly to the Dnm1p homolog Drp1 (14). To gain further insight into the relationship between Pex11p and Dnm1p in H. polymorpha, we subjected lysates of WT, pex11Δ, and dnm1Δ cells to coimmunoprecipitation analysis using anti-Dnm1p antibodies.…”

“…Dnm1p (Drp1 in mammals) (11,14) is a large GTPase that achieves membrane fission by forming oligomeric, ring-like structures around constricted sites on organelle membranes (15). Powered by GTP hydrolysis, these ring-like structures then tighten further until the membrane severs.…”

Peroxisome biogenesis in mammalian cells

“…In mammalian cells, dynamin-like protein 1 (DLP1) (Koch et al, 2003; Li and Gould, 2003; Tanaka et al, 2006; Waterham et al, 2007), fission 1 (Fis1) (Koch et al, 2005; Kobayashi et al, 2007), and mitochondrial fission factor (Mff) (Gandre-Babbe and Van Der Bliek, 2008; Otera et al, 2010; Koch and Brocard, 2012; Itoyama et al, 2013) are shown to be involved in the fission of peroxisomes.…”

Dynamin-related Protein 1 (Drp1) Promotes Structural Intermediates of Membrane Division

“…On the other hand, peroxisomes are ubiquitous subcellular organelles that participate in a variety of important catabolic and anabolic functions, including hydrogen peroxide and lipid metabolism (7). It is thought that peroxisome proliferation also occurs by division, comprising three stages: elongation, constriction, and fission (8).…”