Digest it all: the lysosomal turnover of cytoplasmic aggregates

TY - JOUR

T1 - Digest it all

T2 - the lysosomal turnover of cytoplasmic aggregates

AU - Mauthe, Mario

AU - Kampinga, Harm H

AU - Hipp, Mark S

AU - Reggiori, Fulvio

N1 - Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.

PY - 2023/3

Y1 - 2023/3

N2 - Aggrephagy describes the selective lysosomal transport and turnover of cytoplasmic protein aggregates by macro-autophagy. In this process, protein aggregates and conglomerates are polyubiquitinated and then sequestered by autophagosomes. Soluble selective autophagy receptors (SARs) are central to aggrephagy and physically bind to both ubiquitin and the autophagy machinery, thus linking the cargo to the forming autophagosomal membrane. Because the accumulation of protein aggregates is associated with cytotoxicity in several diseases, a better molecular understanding of aggrephagy might provide a conceptual framework to develop therapeutic strategies aimed at delaying the onset of these pathologies by preventing the buildup of potentially toxic aggregates. We review recent advances in our knowledge about the mechanism of aggrephagy.

AB - Aggrephagy describes the selective lysosomal transport and turnover of cytoplasmic protein aggregates by macro-autophagy. In this process, protein aggregates and conglomerates are polyubiquitinated and then sequestered by autophagosomes. Soluble selective autophagy receptors (SARs) are central to aggrephagy and physically bind to both ubiquitin and the autophagy machinery, thus linking the cargo to the forming autophagosomal membrane. Because the accumulation of protein aggregates is associated with cytotoxicity in several diseases, a better molecular understanding of aggrephagy might provide a conceptual framework to develop therapeutic strategies aimed at delaying the onset of these pathologies by preventing the buildup of potentially toxic aggregates. We review recent advances in our knowledge about the mechanism of aggrephagy.

KW - cellular protein quality control

KW - chaperone-mediated autophagy

KW - macro-autophagy

KW - micro-autophagy

KW - p62 bodies

KW - selective autophagy receptors

KW - Protein Aggregates

KW - Autophagosomes

KW - Sequestosome-1 Protein/metabolism

KW - Lysosomes/metabolism

KW - Autophagy

U2 - 10.1016/j.tibs.2022.09.012

DO - 10.1016/j.tibs.2022.09.012

M3 - Review

C2 - 36280494

SN - 0968-0004

VL - 48

SP - 216

EP - 228

JO - Trends in Biochemical Sciences

JF - Trends in Biochemical Sciences

IS - 3

ER -