PEX16: a multifaceted regulator of peroxisome biogenesis

Peter K Kim,Robert T Mullen

doi:10.3389/fphys.2013.00241

Abstract

Peroxisomes are formed by two distinct pathways: the growth and fission of mature peroxisomes and de novo synthesis at the endoplasmic reticulum (ER). While many of the molecular mechanisms underlying these two pathways remain to be elucidated, it is generally accepted that their relative contribution to peroxisome formation may vary depending on the species, cell type and/or physiological status of the organism. One pertinent example of the apparent differences in the regulation of peroxisome biogenesis among evolutionarily diverse species is the involvement of the peroxin PEX16. In Yarrowia lipolytica, for instance, PEX16 is an intraperoxisomal peripheral membrane protein that participates in peroxisomal fission. By contrast, Human PEX16 is an integral membrane protein that is thought to function at the ER during the early stages of de novo peroxisome formation and also recruits peroxisomal membrane proteins directly to mature peroxisomes. Similarly, PEX16 in the plant Arabidopsis thaliana is speculated to be a PMP receptor at the ER and peroxisomes, and is also required for the formation of other ER-derived organelles, such as oil and protein bodies. Here we briefly review the current knowledge of Y. lipolytica, human and A. thaliana PEX16 in the context of our overall understanding of peroxisome biogenesis and the role of the ER in this process in these three divergent species.

Highlights

Peroxisomes are found in virtually all eukaryotic organisms and while they possess a somewhat simple architecture consisting of a nonhomogenous matrix enclosed by a single membrane, their metabolic functions are highly complex (Islinger et al, 2010)
It is remarkable that some organisms, such as S. cerevisiae, lack a PEX16 homolog (Kiel et al, 2006), yet their mode of peroxisome biogenesis is similar to Y. lipolytica (Van Der Zand et al, 2012), implying that they rely instead on an alternative mechanism(s), or other proteins that provide similar functions, for the control of key steps during peroxisome biogenesis
One possible explanation for this apparent loss of PEX16, at least in S. cerevisiae, is that all of the peroxisomal membrane proteins (PMPs) in this yeast are inserted into the endoplasmic reticulum (ER) via the SEC61 complex (Van Der Zand et al, 2010; Thoms et al, 2012)

Summary

INTRODUCTION

Peroxisomes are found in virtually all eukaryotic organisms and while they possess a somewhat simple architecture consisting of a nonhomogenous matrix enclosed by a single membrane, their metabolic functions are highly complex (Islinger et al, 2010). Over 30 peroxins involved in the key steps underlying peroxisome biogenesis in yeast have been identified, many of which are present in other eukaryotes, including mammals and plants (Hayashi and Nishimura, 2006; Kiel et al, 2006). Pertinent examples of these conserved peroxins include those involved in peroxisomal matrix protein import (PEX5, 7, 10, 12, 13, etc.) and those that help orchestrate the growth and division of peroxisomes (e.g., PEX11 protein family). PEX16 homologs are absent in some well characterized model organisms, including S. cerevisiae (Kiel et al, 2006) and Caenorhabditis elegans (Thieringer et al, 2003)

Kim and Mullen

CONCLUSIONS AND PERSPECTIVES