ESCRT-III is required for scissioning new peroxisomes from the endoplasmic reticulum

• Published in: The Journal of cell biology Vol. 217; no. 6; pp. 2087 - 2102
• Main Authors: Mast, Fred D, Herricks, Thurston, Strehler, Kathleen M, Miller, Leslie R, Saleem, Ramsey A, Rachubinski, Richard A, Aitchison, John D
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 04-06-2018
• Subjects: Biochemistry; Biosynthesis; Cleavage; Cytoplasmic Vesicles - drug effects; Cytoplasmic Vesicles - metabolism; Cytosol; Dynamic control; Endoplasmic reticulum; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - metabolism; Endosomal Sorting Complexes Required for Transport - metabolism; Eukaryotes; Genetic Testing; Genetics; Membrane vesicles; Oleic Acid - pharmacology; Organelle Biogenesis; Peroxisomes; Peroxisomes - drug effects; Peroxisomes - metabolism; Proteins; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; Vesicles
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201706044

Dynamic control of peroxisome proliferation is integral to the peroxisome's many functions. The endoplasmic reticulum (ER) serves as a source of preperoxisomal vesicles (PPVs) that mature into peroxisomes during de novo peroxisome biogenesis and support growth and division of existing peroxisomes. However, the mechanism of PPV formation and release from the ER remains poorly understood. In this study, we show that endosomal sorting complexes required for transport (ESCRT)-III are required to release PPVs budding from the ER into the cytosol. Absence of ESCRT-III proteins impedes de novo peroxisome formation and results in an aberrant peroxisome population in vivo. Using a cell-free PPV budding assay, we show that ESCRT-III proteins Vps20 and Snf7 are necessary to release PPVs from the ER. ESCRT-III is therefore a positive effector of membrane scission for vesicles budding both away from and toward the cytosol. These findings have important implications for the evolutionary timing of emergence of peroxisomes and the rest of the internal membrane architecture of the eukaryotic cell.