Starvation-induced autophagy via calcium-dependent TFEB dephosphorylation is suppressed by Shigyakusan | Zendy

Sumiko Ikari | Zendy; Shiou-Ling Lu | Zendy; Feike Hao | Zendy; Kenta Imai | Zendy; Yasuhiro Araki | Zendy; Yohei Yamamoto | Zendy; ChaoYuan Tsai | Zendy; Yumi Nishiyama | Zendy; Nobukazu Shitan | Zendy; Tamotsu Yoshimori | Zendy; Takanobu Otomo | Zendy; Takeshi Noda | Zendy

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Starvation-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,

ChaoYuan 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.

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