テラワキ セイゴウ   Seigo Terawaki
  寺脇 正剛
   所属   川崎医科大学  医学部 基礎医学 分子遺伝医学
   職種   特任講師
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 LC3 lipidation is essential for TFEB activation during the lysosomal damage response to kidney injury.
掲載誌名 正式名:Nature cell biology
略  称:Nat Cell Biol
ISSNコード:14764679/14657392
掲載区分国外
巻・号・頁 22(10),1252-1263頁
著者・共著者 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
発行年月 2020/10
概要 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