Mitochondrial respiration supports autophagy to provide stress resistance during quiescence

0557875 - BTÚ 2023 RIV US eng J - Journal Article
Magalhaes-Novais, Silvia - Blecha, Jan - Naraine, Ravindra - Mikesova, Jana - Abaffy, Pavel - Pecinová, Alena - Miloševič, Mirko - Bohuslavová, Romana - Procházka, Jan - Khan, S. - Novotná, Eliška - Šindelka, Radek - Machan, R. - Dewerchin, M. - Vlčák, Erik - Kalucka, J. - Štemberková-Hubáčková, Soňa - Benda, A. - Goveia, J. - Mráček, Tomáš - Bařinka, Cyril - Carmeliet, P. - Neužil, Jiří - Rohlenová, Kateřina - Rohlena, Jakub
Mitochondrial respiration supports autophagy to provide stress resistance during quiescence.
Autophagy. Roč. 18, č. 10 (2022), s. 2409-2426. ISSN 1554-8627. E-ISSN 1554-8635
R&D Projects: GA ČR(CZ) GA20-18513S; GA ČR GA17-24441S; GA ČR(CZ) GA20-05942S; GA ČR(CZ) GA18-02550S; GA ČR(CZ) GX21-04607X; GA ČR(CZ) GA22-34507S; GA MZd(CZ) NV17-30138A; GA MZd(CZ) NV17-32727A; GA MZd(CZ) NU21-03-00545; GA MZd(CZ) NU20J-02-00035; GA MŠMT(CZ) LM2018129; GA MŠMT(CZ) LM2015040; GA MŠMT(CZ) LM2018126; GA MŠMT EF18_046/0015861; GA MŠMT(CZ) EF16_013/0001775; GA MŠMT(CZ) EF18_046/0016045
Research Infrastructure: Czech-BioImaging II - 90129; CCP II - 90126
Institutional support: RVO:86652036 ; RVO:68378050 ; RVO:67985823
Keywords : ATG4B * cell death * biosynthesis * electron transport chain
OECD category: Cell biology
Impact factor: 13.3, year: 2022
Method of publishing: Open access
https://www.tandfonline.com/doi/full/10.1080/15548627.2022.2038898

Mitochondrial oxidative phosphorylation (OXPHOS) generates ATP, but OXPHOS also supports biosynthesis during proliferation. In contrast, the role of OXPHOS during quiescence, beyond ATP production, is not well understood. Using mouse models of inducible OXPHOS deficiency in all cell types or specifically in the vascular endothelium that negligibly relies on OXPHOS-derived ATP, we show that selectively during quiescence OXPHOS provides oxidative stress resistance by supporting macroautophagy/autophagy. Mechanistically, OXPHOS constitutively generates low levels of endogenous ROS that induce autophagy via attenuation of ATG4B activity, which provides protection from ROS insult. Physiologically, the OXPHOS-autophagy system (i) protects healthy tissue from toxicity of ROS-based anticancer therapy, and (ii) provides ROS resistance in the endothelium, ameliorating systemic LPS-induced inflammation as well as inflammatory bowel disease. Hence, cells acquired mitochondria during evolution to profit from oxidative metabolism, but also built in an autophagy-based ROS-induced protective mechanism to guard against oxidative stress associated with OXPHOS function during quiescence.
Permanent Link: http://hdl.handle.net/11104/0331732