Dataset Information

Mitochondrial respiration is necessary to combat oxidative stress in quiescent cells

ABSTRACT: Mitochondrial oxidative phosphorylation (OXPHOS) makes ATP and supports biosynthesis during proliferation, but its role in non-proliferating cells, beyond ATP production, is less understood. Here we show that OXPHOS protects quiescent (but not proliferating) cells from oxidative stress. Using in vivo models of OXPHOS deficiency (whole body and endothelium-specific) we show that OXPHOS mediated resistance to ROS (i) maintains selectivity of ROS-based anticancer therapy by protecting normal tissues during treatment, and in quiescent endothelium (ii) ameliorates systemic LPS-induced inflammation and (iii) attenuates symptoms of the inflammatory bowel disease. ROS-resistance provided by OXPHOS is independent of its role in biosynthesis or NADH recycling. Instead, in quiescent cells OXPHOS constitutively generates low levels of endogenous ROS that support basal autophagic flux and protect from exogenous ROS challenge. Hence, during evolution cells acquired mitochondria to profit from oxidative metabolism, but also built in an OXPHOS-dependent mechanism to guard against the resulting oxidative stress.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Karel Harant

LAB HEAD: Jakub Rohlena

PROVIDER: PXD021376 | Pride | 2022-10-13

REPOSITORIES: Pride

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Mitochondrial respiration supports autophagy to provide stress resistance during quiescence.

Magalhaes-Novais Silvia S Blecha Jan J Naraine Ravindra R Mikesova Jana J Abaffy Pavel P Pecinova Alena A Milosevic Mirko M Bohuslavova Romana R Prochazka Jan J Khan Shawez S Novotna Eliska E Sindelka Radek R Machan Radek R Dewerchin Mieke M Vlcak Erik E Kalucka Joanna J Stemberkova Hubackova Sona S Benda Ales A Goveia Jermaine J Mracek Tomas T Barinka Cyril C Carmeliet Peter P Neuzil Jiri J Rohlenova Katerina K Rohlena Jakub J

Autophagy 20220308 10

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/auto ...[more]

PMID: 35258392

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	allSpectra.HCD.ITMS.iso_0.apl	Other
	allSpectra.HCD.ITMS.iso_1.apl	Other