Abstract
Lipid droplets (LDs) and peroxisomes are ubiquitous organelles with central roles in eukaryotic cells. Although the mechanisms involved in biogenesis of these organelles remain elusive, both seem to require the endoplasmic reticulum (ER). Here we show that in yeast the ER budding of these structurally unrelated organelles has remarkably similar requirements and involves cooperation between Pex30 and the seipin complex. In the absence of these components, budding of both LDs and peroxisomes is inhibited, leading to the ER accumulation of their respective constituent molecules, such as triacylglycerols and peroxisomal membrane proteins, whereas COPII vesicle formation remains unaffected. This phenotype can be reversed by remodeling ER phospholipid composition highlighting a key function of these lipids in organelle biogenesis. We propose that seipin and Pex30 act in concert to organize membrane domains permissive for organelle budding, and that may have a lipid composition distinct from the bulk ER.
Highlights
Lipid droplets (LDs) and peroxisomes are ubiquitous organelles with central roles in eukaryotic cells
We present evidence that pre-peroxisomal vesicles (PPVs), which originate peroxisomes, and LDs bud from similar endoplasmic reticulum (ER) domains through a process requiring the cooperation between seipin and Pex[30]
Simultaneous deletion of these components largely inhibits budding of LDs and PPVs, indicating their partly redundant roles in organelle biogenesis
Summary
Lipid droplets (LDs) and peroxisomes are ubiquitous organelles with central roles in eukaryotic cells. In the absence of these components, budding of both LDs and peroxisomes is inhibited, leading to the ER accumulation of their respective constituent molecules, such as triacylglycerols and peroxisomal membrane proteins, whereas COPII vesicle formation remains unaffected This phenotype can be reversed by remodeling ER phospholipid composition highlighting a key function of these lipids in organelle biogenesis. The mechanisms of COPII vesicle formation are well characterized, how specific proteins and lipids in the ER give rise to other organelles, such as lipid droplets (LDs) and peroxisomes, remains largely unknown[2] These are ubiquitous organelles and mutations impairing their functions result in devastating diseases[3,4]. De novo peroxisome biogenesis involves the budding of membrane-bound pre-peroxisomal vesicles (PPVs) from specific ER domains distinct from COPII assembly sites[5,6]. Factors that cooperate with seipin have not been identified and, as in the case of PPVs, the precise composition of LD budding sites is unclear
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