Lipid Droplet and Peroxisome Biogenesis: Do They Go Hand-in-Hand?

Abstract

All eukaryotic cells contain membrane bound structures called organelles. Each organelle has specific composition and function. Some of the organelles are generated de novo in a cell. The endoplasmic reticulum (ER) is a major contributor of proteins and membranes for most of the organelles. In this mini review, we discuss de novo biogenesis of two such organelles, peroxisomes and lipid droplets (LDs), that are formed in the ER membrane. LDs and peroxisomes are highly conserved ubiquitously present membrane-bound organelles. Both these organelles play vital roles in lipid metabolism and human health. Here, we discuss the current understanding of de novo biogenesis of LDs and peroxisomes, recent advances on how biogenesis of both the organelles might be linked, physical interaction between LDs and peroxisomes and other organelles, and their physiological importance.

Keywords: lipid droplet; lipid metabolism; membrane trafficking; organelle biogenesis; peroxisome.

FIGURE 1

(A) De novo peroxisome biogenesis in yeast and mammalian cells. PPVs containing the docking complex proteins are generated independently of Pex3 and Pex19 at ER subdomains containing Pex30. PPVs containing ring complex proteins are generated in a Pex3- and Pex19-dependent manner. ESCRT-III complex is required for scission of PPVs from the ER membrane. The two pools of PPVs fuse to form an import competent mature peroxisome. In mammals, Pex16-containing PPVs from ER and Pex3 and Pex14-containing PPVs from mitochondrial outer membrane fuse to form a functional peroxisome. (B) Lipid droplet biogenesis. Neutral lipid synthesizing enzymes generate sterol esters (SE) and triglycerides (TG) to form a lens-like structure in the lipid bilayer. The ER regions are enriched with seipin, FIT proteins, and Pex30/MCTP2. As the lens grows the LD buds into the cytoplasm. In yeast, LDs remain attached to the ER subdomains containing Pex30/MCTP2 and seipin but no FIT proteins.

FIGURE 2

Link between peroxisome and LD biogenesis: The formation of new Pex14-containing PPVs and LDs occur at the same ER subdomains, which are positive for Pex30/MCTP2 proteins. Mature peroxisomes also physically associate with LDs. Tethers identified so far include ABCD1 on peroxisomes, which interacts with Spastin on LDs. Other tethers may also be involved in peroxisome-LD contacts. Pex19 is a cytosolic protein required for peroxisomal protein targeting, which when farnesylated targets a LD protein UBXD8 to LDs.