Graduate School of Frontier Biosciences, Osaka University

Japanese

Autophagy sequesters damaged lysosomes to control lysosomal biogenesis and kidney injury

Journal EMBO J (2013) in press
Authors Ikuko Maejima (1, 8), Atsushi Takahashi (2), Hiroko Omori (3), Tomonori Kimura (2), Yoshitsugu Takabatake (2), Tatsuya Saitoh (4), Akitsugu Yamamoto (5), Maho Hamasaki (1), Takeshi Noda (6), Yoshitaka Isaka (2) and Tamotsu Yoshimori (1, 7, 8)

  1. Department of Genetics, Graduate School of Medicine, Osaka University, Osaka, Japan
  2. Department of Geriatric Medicine and Nephrology, Graduate School of Medicine, Osaka University, Osaka, Japan
  3. Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
  4. Laboratory of Host Defense, WPI Immunology Frontier Research Center (IFReC), Osaka University, Osaka, Japan
  5. Faculty of Bioscience, Nagahama Institute of BioScience and Technology, Shiga, Japan
  6. Center for Frontier Oral Science, Graduate School of Dentistry, Osaka University, Osaka, Japan
  7. Laboratory of Intracellular Membrane Dynamics, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan
  8. Japan Science and Technology Agency CREST, Tokyo, Japan
Title Autophagy sequesters damaged lysosomes to control lysosomal biogenesis and kidney injury
PubMed 23921551
Laboratory Laboratory of Intracellular Membrane Dynamics 〈Prof. Yoshimori〉
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-Lleucine 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.