Mitochondrial ROS-derived PTEN oxidation activates PI3K pathway for mTOR-induced myogenic autophagy. Issue 11 (November 2018)

• Record Type: Journal Article
• Authors: Kim, Jin-Hwan; Choi, Tae; Park, Seolhui; Yun, Hyeong; Nguyen, Ngoc; Jo, Yong; Jang, Miran; Kim, Jieun; Kim, Joungmok; Kang, Insug; Ha, Joohun; Murphy, Michael; Tang, Dean; Kim, Sung
• Is Part Of: Cell death and differentiation. Volume 25:Issue 11(2018)
• Page Start: 1921
• Page End: 1937
• Publication Date: 2018-11
• Subjects: Cell death -- Periodicals; Cell differentiation -- Periodicals; 571.835
• DOI: 10.1038/s41418-018-0165-9
• Languages: English
• ISSNs: 1350-9047

Abstract

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.