Open AccessStarvation-induced autophagy via calcium-dependent TFEB dephosphorylation is suppressed by Shigyakusan
Author(s) -
Sumiko Ikari,
Shiou-Ling Lu,
Feike Hao,
Kenta Imai,
Yasuhiro Araki,
Yohei Yamamoto,
ChangYouh Tsai,
Yumi Nishiyama,
Nobukazu Shitan,
Tamotsu Yoshimori,
Takanobu Otomo,
Takeshi Noda
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0230156
Subject(s) - autophagy , kampo , tfeb , ulk1 , dephosphorylation , starvation , medicine , phosphorylation , microbiology and biotechnology , pharmacology , ampk , chemistry , biology , biochemistry , protein kinase a , apoptosis , pathology , alternative medicine , phosphatase
Kampo, a system of traditional Japanese therapy utilizing mixtures of herbal medicine, is widely accepted in the Japanese medical system. Kampo originated from traditional Chinese medicine, and was gradually adopted into a Japanese style. Although its effects on a variety of diseases are appreciated, the underlying mechanisms remain mostly unclear. Using a quantitative tf-LC3 system, we conducted a high-throughput screen of 128 kinds of Kampo to evaluate the effects on autophagy. The results revealed a suppressive effect of Shigyakusan/TJ-35 on autophagic activity. TJ-35 specifically suppressed dephosphorylation of ULK1 and TFEB, among several TORC1 substrates, in response to nutrient deprivation. TFEB was dephosphorylated by calcineurin in a Ca 2+ dependent manner. Cytosolic Ca 2+ concentration was increased in response to nutrient starvation, and TJ-35 suppressed this increase. Thus, TJ-35 prevents the starvation-induced Ca 2+ increase, thereby suppressing induction of autophagy.