Mitochondrial ROS-derived PTEN oxidation activates PI3K pathway for mTOR-induced myogenic autophagy.

TitleMitochondrial ROS-derived PTEN oxidation activates PI3K pathway for mTOR-induced myogenic autophagy.
Publication TypeJournal Article
Year of Publication2018
AuthorsKim, J-H, Choi, TGyu, Park, S, Yun, HRok, Nguyen, NNgo Yen, Jo, YHwa, Jang, M, Kim, J, Kim, J, Kang, I, Ha, J, Murphy, MP, Tang, DG, Kim, SSoo
JournalCell Death Differ
Date Published2018 Jul 24
ISSN1476-5403
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.

DOI10.1038/s41418-018-0165-9
Alternate JournalCell Death Differ.
Citation Key10.1038/s41418-018-0165-9
PubMed ID30042494
Grant ListNRF-2011-0030072 / / National Research Foundation of Korea (NRF) /
NRF-2017R1A2B2007870 / / National Research Foundation of Korea (NRF) /
NRF-2016R1D1A1B03933763 / / National Research Foundation of Korea (NRF) /