RT Journal Article
SR Electronic
T1 ESCRT-III acts in scissioning new peroxisomes from the ER
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 147603
DO 10.1101/147603
A1 Fred D. Mast
A1 Thurston Herricks
A1 Kathleen M. Strehler
A1 Leslie R. Miller
A1 Ramsey A. Saleem
A1 Richard R. Rachubinski
A1 John D. Aitchison
YR 2017
UL http://biorxiv.org/content/early/2017/06/07/147603.abstract
AB Dynamic control of proliferation is integral to the peroxisome’s many functions. A breakdown in the ability of cells to form peroxisomes is linked to many human health issues, including defense against infectious agents, cancer, aging, heart disease, obesity and diabetes, and forms the basis of a spectrum of genetic disorders that cause severe neuropathologies. The endoplasmic reticulum (ER) serves as a source for preperoxisomal vesicles (PPVs) that mature into peroxisomes during de novo peroxisome biogenesis and to support growth and division of existing peroxisomes. However, the mechanism of PPV formation and release from the ER remains poorly understood. Here we show that the evolutionarily ancient endosomal sorting complexes required for transport (ESCRT)-III are peroxisome biogenesis factors that function to cleave PPVs budding from the ER into the cytosol. Using comprehensive morphological and genetic assays of peroxisome formation and function we find that 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 required to release PPVs from the ER. ESCRT-III is therefore a positive effector of membrane scission for vesicles budding both away from and towards the cytosol, a finding that has clear implications for the evolutionary timing of emergence of peroxisomes and the rest of the internal membrane architecture of the eukaryotic cell.