Endonuclease G promotes autophagy by suppressing mTOR signaling and activating the DNA damage response

Wenjun Wang, Jianshuang Li, Junyang Tan, Miaomiao Wang, Jing Yang, Zhi-Min Zhang, Chuanzhou Li, Alexei G. Basnakian, Hong-Wen Tang, Norbert Perrimon and Qinghua Zhou ()
Additional contact information
Wenjun Wang: Jinan University
Jianshuang Li: Zhuhai Institute of Translational Medicine Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University
Junyang Tan: Jinan University
Miaomiao Wang: Jinan University
Jing Yang: Jinan University
Zhi-Min Zhang: Jinan University
Chuanzhou Li: Huazhong University of Science and Technology
Alexei G. Basnakian: University of Arkansas for Medical Sciences
Hong-Wen Tang: Duke-NUS Medical School
Norbert Perrimon: Harvard Medical School
Qinghua Zhou: Jinan University

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract Endonuclease G (ENDOG), a mitochondrial nuclease, is known to participate in many cellular processes, including apoptosis and paternal mitochondrial elimination, while its role in autophagy remains unclear. Here, we report that ENDOG released from mitochondria promotes autophagy during starvation, which we find to be evolutionally conserved across species by performing experiments in human cell lines, mice, Drosophila and C. elegans. Under starvation, Glycogen synthase kinase 3 beta-mediated phosphorylation of ENDOG at Thr-128 and Ser-288 enhances its interaction with 14-3-3γ, which leads to the release of Tuberin (TSC2) and Phosphatidylinositol 3-kinase catalytic subunit type 3 (Vps34) from 14-3-3γ, followed by mTOR pathway suppression and autophagy initiation. Alternatively, ENDOG activates DNA damage response and triggers autophagy through its endonuclease activity. Our results demonstrate that ENDOG is a crucial regulator of autophagy, manifested by phosphorylation-mediated interaction with 14-3-3γ, and its endonuclease activity-mediated DNA damage response.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-20780-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20780-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-20780-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().