Mitochondrial ROS-derived PTEN Oxidation Activates PI3K Pathway for MTOR-induced Myogenic Autophagy

Overview

Journal Cell Death Differ

Specialty Cell Biology

Date 2018 Jul 26

PMID 30042494

Citations 64

Authors

Jin-Hwan Kim

Tae Gyu Choi

Seolhui Park

Hyeong Rok Yun

Ngoc Ngo Yen Nguyen

Yong Hwa Jo

Miran Jang

Jieun Kim

Joungmok Kim

Insug Kang

Joohun Ha

Michael P Murphy

Dean G Tang

Sung Soo Kim

Affiliations

Soon will be listed here.

Abstract

Muscle differentiation is a crucial process controlling muscle development and homeostasis. Mitochondrial reactive oxygen species (mtROS) rapidly increase and function as critical cell signaling intermediates during the muscle differentiation. However, it has not yet been elucidated how they control myogenic signaling. Autophagy, a lysosome-mediated degradation pathway, is importantly recognized as intracellular remodeling mechanism of cellular organelles during muscle differentiation. Here, we demonstrated that the mtROS stimulated phosphatidylinositol 3 kinase/AKT/mammalian target of rapamycin (mTOR) cascade, and the activated mTORC1 subsequently induced autophagic signaling via phosphorylation of uncoordinated-51-like kinase 1 (ULK1) at serine 317 and upregulation of Atg proteins to prompt muscle differentiation. Treatment with MitoQ or rapamycin impaired both phosphorylation of ULK1 and expression of Atg proteins. Therefore, we propose a novel regulatory paradigm in which mtROS are required to initiate autophagic reconstruction of cellular organization through mTOR activation in muscle differentiation.

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