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Autophagy sequesters damaged lysosomes to control lysosomal biogenesis and kidney injury
Author(s) -
Maejima Ikuko,
Takahashi Atsushi,
Omori Hiroko,
Kimura Tomonori,
Takabatake Yoshitsugu,
Saitoh Tatsuya,
Yamamoto Akitsugu,
Hamasaki Maho,
Noda Takeshi,
Isaka Yoshitaka,
Yoshimori Tamotsu
Publication year - 2013
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2013.171
Subject(s) - biology , autophagy , biogenesis , tfeb , microbiology and biotechnology , lysosome , biochemistry , enzyme , gene , apoptosis
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.