Autophagy Is Essential for Neural Stem Cell Proliferation Promoted by Hypoxia

• DOI: 10.1093/stmcls/sxac076
• Publication Date: 2022-10-08T14:07:32Z
• Authors: Jian Li; Sheng-Hui Gong; Yun-Ling He; Yan Cao; Ying Chen; Guang-Hai Huang; Yu-Fei Wang; Ming Zhao; Xiang Cheng; Yan-Zhao Zhou; Tong Zhao; Yong-Qi Zhao; Ming Fan; Hai-Tao Wu; Ling-Ling Zhu; Li-Ying Wu
• Keywords: RHEB; Hypoxia

Abstract Hypoxia as a microenvironment or niche stimulates proliferation of neural stem cells (NSCs). However, the underlying mechanisms remain elusive. Autophagy is protective mechanism by which recycled cellular components and energy are rapidly supplied to cell under stress. Whether autophagy mediates NSCs hypoxia how induces unclear. Here, we report that facilitates embryonic NSC through HIF-1/mTORC1 signaling pathway-mediated autophagy. Initially, found greatly induced in NSCs, while inhibition severely impeded conditions. Next, demonstrated core regulator HIF-1 was necessary sufficient for induction NSCs. Considering mTORC1 key switch suppresses autophagy, subsequently analyzed effect on activity. Our results showed activity negatively regulated HIF-1. Finally, provided evidence via its downstream target gene BNIP3. The increased expression BNIP3 enhanced mediated repressing mTORC1. We further illustrated can interact with Rheb, canonical activator Thus, suppose interaction Rheb reduces regulation toward activity, relieves suppression thereby promoting rapid Altogether, this study identified new HIF-1/BNIP3-Rheb/mTORC1 axis, regulates