Autophagy Sequesters Damaged Lysosomes to Control Lysosomal Biogenesis and Kidney Injury

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2013 Aug 8

PMID 23921551

Citations 314

Authors

Ikuko Maejima

Atsushi Takahashi

Hiroko Omori

Tomonori Kimura

Yoshitsugu Takabatake

Tatsuya Saitoh

Akitsugu Yamamoto

Maho Hamasaki

Takeshi Noda

Yoshitaka Isaka

Tamotsu Yoshimori

Affiliations

Soon will be listed here.

Abstract

Diverse causes, including pathogenic invasion or the uptake of mineral crystals such as silica and monosodium urate (MSU), threaten cells with lysosomal rupture, which can lead to oxidative stress, inflammation, and apoptosis or necrosis. Here, we demonstrate that lysosomes are selectively sequestered by autophagy, when damaged by MSU, silica, or the lysosomotropic reagent L-Leucyl-L-leucine methyl ester (LLOMe). Autophagic machinery is recruited only on damaged lysosomes, which are then engulfed by autophagosomes. In an autophagy-dependent manner, low pH and degradation capacity of damaged lysosomes are recovered. Under conditions of lysosomal damage, loss of autophagy causes inhibition of lysosomal biogenesis in vitro and deterioration of acute kidney injury in vivo. Thus, we propose that sequestration of damaged lysosomes by autophagy is indispensable for cellular and tissue homeostasis.

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