Ravasz 2024 Sci Rep

From Bioblast
Publications in the MiPMap
Ravasz D, Bui D, Nazarian S, Pallag G, Karnok N, Roberts J, Marzullo BP, Tennant DA, Greenwood B, Kitayev A, Hill C, KomlΓ³di T, Doerrier C, Cunatova K, Fernandez-Vizarra E, Gnaiger E, Kiebish Michael A, Raska A, Kolev K, Czumbel B, Narain NR, Seyfried TN, Chinopoulos C (2024) Residual Complex I activity and amphidirectional Complex II operation support glutamate catabolism through mtSLP in anoxia. Sci Rep 14:1729. https://doi.org/10.1038/s41598-024-51365-4

Β» PMID: 38242919 Open Access

Ravasz Dora, Bui D, Nazarian S, Pallag Gergely, Karnok N, Roberts J, Marzullo BP, Tennant DA, Greenwood B, Kitayev A, Hill C, Komlodi Timea, Doerrier Carolina, Cunatova K, Fernandez-Vizarra Erika, Gnaiger Erich, Kiebish MA, Raska A, Kolev K, Czumbel B, Narain Niven R, Seyfried TN, Chinopoulos Christos (2024) Sci Rep

Abstract: Anoxia halts oxidative phosphorylation (OXPHOS) causing an accumulation of reduced compounds in the mitochondrial matrix which impedes dehydrogenases. By simultaneously measuring oxygen concentration, NADH autofluorescence, mitochondrial membrane potential and ubiquinone reduction extent in isolated mitochondria in real-time, we demonstrate that Complex I utilized endogenous quinones to oxidize NADH under acute anoxia. 13C metabolic tracing or untargeted analysis of metabolites extracted during anoxia in the presence or absence of site-specific inhibitors of the electron transfer system showed that NAD+ regenerated by Complex I is reduced by the 2-oxoglutarate dehydrogenase Complex yielding succinyl-CoA supporting mitochondrial substrate-level phosphorylation (mtSLP), releasing succinate. Complex II operated amphidirectionally during the anoxic event, providing quinones to Complex I and reducing fumarate to succinate. Our results highlight the importance of quinone provision to Complex I oxidizing NADH maintaining glutamate catabolism and mtSLP in the absence of OXPHOS.

β€’ Bioblast editor: Gnaiger E β€’ O2k-Network Lab: AT Innsbruck Oroboros, IT Padova Viscomi C, HU Budapest Tretter L, HU Budapest Chinopoulos C

Labels: MiParea: Respiration 

Stress:Hypoxia  Organism: Mouse  Tissue;cell: Heart, Liver  Preparation: Isolated mitochondria 

Regulation: mt-Membrane potential, Redox state  Coupling state: OXPHOS  Pathway: N, S  HRR: Oxygraph-2k, O2k-Fluorometer, NextGen-O2k 

Rhodamine 123 

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