Lipid droplet and peroxisome biogenesis occur at the same ER subdomains

Amit S Joshi,Tim P Levine,Andy Golden,Benjamin Nebenfuehr,Prasanna Satpute-Krishnan,Vineet Choudhary,William A Prinz

doi:10.1038/s41467-018-05277-3

Abstract

Nascent lipid droplet (LD) formation occurs in the endoplasmic reticulum (ER) membrane but it is not known how sites of biogenesis are determined. We previously identified ER domains in S. cerevisiae containing the reticulon homology domain (RHD) protein Pex30 that are regions where preperoxisomal vesicles (PPVs) form. Here, we show that Pex30 domains are also sites where most nascent LDs form. Mature LDs usually remain associated with Pex30 subdomains, and the same Pex30 subdomain can simultaneously associate with a LD and a PPV or peroxisome. We find that in higher eukaryotes multiple C2 domain containing transmembrane protein (MCTP2) is similar to Pex30: it contains an RHD and resides in ER domains where most nascent LD biogenesis occurs and that often associate with peroxisomes. Together, these findings indicate that most LDs and PPVs form and remain associated with conserved ER subdomains, and suggest a link between LD and peroxisome biogenesis.

Highlights

Nascent lipid droplet (LD) formation occurs in the endoplasmic reticulum (ER) membrane but it is not known how sites of biogenesis are determined
In this study, we demonstrate that conserved ER subdomains with specialized reticulon homology domain (RHD)-containing proteins are sites where nascent LDs mature
Consistent with this, we found that these sites, in S. cerevisiae, are enriched in the TAG precursor DAG and are often associated with Nem[1] and Sei[1], proteins previously shown to be enriched at sites of LD biogenesis[13,32,33]

Summary

Introduction

Nascent lipid droplet (LD) formation occurs in the endoplasmic reticulum (ER) membrane but it is not known how sites of biogenesis are determined. We find that in higher eukaryotes multiple C2 domain containing transmembrane protein (MCTP2) is similar to Pex[30]: it contains an RHD and resides in ER domains where most nascent LD biogenesis occurs and that often associate with peroxisomes. Together, these findings indicate that most LDs and PPVs form and remain associated with conserved ER subdomains, and suggest a link between LD and peroxisome biogenesis. Pex[30] has been suggested to reside at ERperoxisome contacts[20,21]

Methods

Results

Conclusion