Mff functions with Pex11pβ and DLP1 in peroxisomal fission

TLDR

Peroxisomal division proceeds through elongation, constriction, and fission and requires translocation of the dynamin‑like protein DLP1 to peroxisomes, yet the targeting machinery is unknown. The study examined whether the mitochondrial fission factor Mff, which recruits DLP1 to mitochondria, also directs DLP1 to peroxisomes. Mff localizes to peroxisomes, and its knockdown blocks peroxisomal fission and DLP1 recruitment, while overexpression enhances DLP1 targeting, peroxisome abundance, and interaction with Pex11β, showing that Mff is essential for peroxisomal DLP1 recruitment and fission.

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.