Seigo Terawaki
   Department   Kawasaki Medical School  Kawasaki Medical School, Department of Molecular and Genetic Medicine,
   Position   Assistant Professor with Special Assignment
Article types 原著
Language English
Peer review Peer reviewed
Title LC3 lipidation is essential for TFEB activation during the lysosomal damage response to kidney injury.
Journal Formal name：Nature cell biology
Abbreviation：Nat Cell Biol
ISSN code：14764679/14657392
Domestic / ForeginForegin
Volume, Issue, Page 22(10),pp.1252-1263
Author and coauthor Nakamura Shuhei, Shigeyama Saki, Minami Satoshi, Shima Takayuki, Akayama Shiori, Matsuda Tomoki, Esposito Alessandra, Napolitano Gennaro, Kuma Akiko, Namba-Hamano Tomoko, Nakamura Jun, Yamamoto Kenichi, Sasai Miwa, Tokumura Ayaka, Miyamoto Mika, Oe Yukako, Fujita Toshiharu, Terawaki Seigo, Takahashi Atsushi, Hamasaki Maho, Yamamoto Masahiro, Okada Yukinori, Komatsu Masaaki, Nagai Takeharu, Takabatake Yoshitsugu, Xu Haoxing, Isaka Yoshitaka, Ballabio Andrea, Yoshimori Tamotsu
Publication date 2020/10
Summary Sensing and clearance of dysfunctional lysosomes is critical for cellular homeostasis. Here we show that transcription factor EB (TFEB)-a master transcriptional regulator of lysosomal biogenesis and autophagy-is activated during the lysosomal damage response, and its activation is dependent on the function of the ATG conjugation system, which mediates LC3 lipidation. In addition, lysosomal damage triggers LC3 recruitment on lysosomes, where lipidated LC3 interacts with the lysosomal calcium channel TRPML1, facilitating calcium efflux essential for TFEB activation. Furthermore, we demonstrate the presence and importance of this TFEB activation mechanism in kidneys in a mouse model of oxalate nephropathy accompanying lysosomal damage. A proximal tubule-specific TFEB-knockout mouse exhibited progression of kidney injury induced by oxalate crystals. Together, our results reveal unexpected mechanisms of TFEB activation by LC3 lipidation and their physiological relevance during the lysosomal damage response.
DOI 10.1038/s41556-020-00583-9
PMID 32989250