The Dynamin-like GTPase DLP1 Is Essential for Peroxisome Division and Is Recruited to Peroxisomes in Part by PEX11

Xiaoling Li,Stephen J Gould

doi:10.1074/jbc.m212031200

Xiaoling Li, Stephen J Gould

Open Access

https://doi.org/10.1074/jbc.m212031200

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Abstract

Peroxisome division involves the conserved PEX11 peroxisomal membrane proteins and in yeast has been shown to require Vps1p, a dynamin-like protein. We show here that DLP1, the human homolog of the yeast DNM1 and VPS1 genes, plays an important role in peroxisome division in human cells. Disruption of DLP1 function by either RNA interference or overexpressing dominant negative DLP1 mutants causes a dramatic reduction in peroxisome abundance, although overexpression of functional DLP1 has no effect on peroxisome abundance. Overexpression of PEX11 induces peroxisome division in a multistep process involving elongation of preexisting peroxisomes followed by their division. We find that DLP1 is dispensable for the first phase of this process but essential for the second. Furthermore, we show that DLP1 associates with peroxisomes and that PEX11 overexpression recruits DLP1 to peroxisome membranes. However, we were unable to detect physical interaction between PEX11 and DLP1, and the stoichiometry of PEX11 and peroxisome-associated DLP1 was far less than 1:1. Based on these and other aspects, we propose that DLP1 performs an essential but transient role in peroxisome division and that PEX11 promotes peroxisome division by recruiting DLP1 to peroxisome membranes through an indirect mechanism.

Highlights

The regulation of organelle abundance involves a complex interplay of organelle synthesis and destruction
To test whether a similar process exists in mammalian cells and to determine further whether this is related to PEX11-mediated peroxisome division, we studied the role of human DLP1 in peroxisome biogenesis
Reduced DLP1 Levels Cause Reduced Peroxisome Abundance—The observation that yeast Vps1p participates in peroxisome membrane division suggested that the human ortholog of Vps1p could have a similar role

Summary

Introduction

The regulation of organelle abundance involves a complex interplay of organelle synthesis and destruction. Peroxisome division involves the conserved PEX11 peroxisomal membrane proteins and in yeast has been shown to require Vps1p, a dynamin-like protein. Yeast vps1 null mutants contain only one or two large peroxisomes and cannot increase peroxisome abundance under conditions that normally induce PEX11 expression and promote peroxisome division [19].

Results

Conclusion