Dynamin-like Protein 1 Is Involved in Peroxisomal Fission

Annett Koch,Meinolf Thiemann,Markus Grabenbauer,Yisang Yoon,Mark A Mcniven,Michael Schrader

doi:10.1074/jbc.m211761200

Abstract

The mammalian dynamin-like protein 1 (DLP1), a member of the dynamin family of large GTPases, possesses mechanochemical properties known to constrict and tubulate membranes. In this study, we have combined two experimental approaches, induction of peroxisome proliferation by Pex11pbeta and expression of dominant-negative mutants, to test whether DLP1 plays a role in peroxisomal growth and division. We were able to localize DLP1 in spots on tubular peroxisomes in HepG2 cells. In addition, immunoblot analysis revealed the presence of DLP1 in highly purified peroxisomal fractions from rat liver and an increase of DLP1 after treatment of rats with the peroxisome proliferator bezafibrate. Expression of a dominant negative DLP1 mutant deficient in GTP hydrolysis (K38A) either alone or in combination with Pex11pbeta caused the appearance of tubular peroxisomes but had no influence on their intracellular distribution. In co-expressing cells, the formation of tubulo-reticular networks of peroxisomes was promoted, and peroxisomal division was completely inhibited. These findings were confirmed by silencing of DLP1 using siRNA. We propose a direct role for the dynamin-like protein DLP1 in peroxisomal fission and in the maintenance of peroxisomal morphology in mammalian cells.

Highlights

Peroxisomes are ubiquitous subcellular organelles that participate in a variety of important catabolic and anabolic functions, including hydrogen peroxide metabolism, the ␤-oxidation of fatty acids, and the biosynthesis of ether phospholipids [1]
We propose a direct role for the dynamin-like protein dynamin-like protein 1 (DLP1) in peroxisomal fission and in the maintenance of peroxisomal morphology in mammalian cells
A Dynamin Protein on Peroxisomes tubulation of peroxisomes. These findings provide the first evidence suggesting that a dynamin-like protein, DLP1, is involved in peroxisomal fission and in the maintenance of peroxisomal morphology in mammalian cells

Summary

Introduction

Peroxisomes are ubiquitous subcellular organelles that participate in a variety of important catabolic and anabolic functions, including hydrogen peroxide metabolism, the ␤-oxidation of fatty acids, and the biosynthesis of ether phospholipids [1]. We propose a direct role for the dynamin-like protein DLP1 in peroxisomal fission and in the maintenance of peroxisomal morphology in mammalian cells. These findings provide the first evidence suggesting that a dynamin-like protein, DLP1, is involved in peroxisomal fission and in the maintenance of peroxisomal morphology in mammalian cells.

Results

Conclusion