PhD Scientific Days 2023

Pharmaceutical Sciences - Posters E

MDH2 reducing oxaloacetate to malate provides NAD+ to KGDHC during respiratory arrest supporting glutaminolysis and mitochondrial substrate-level phosphorylation

Előadó neve

Dr. Nazarian, Sara

Neptun code

EXWWUE

Előadó munkahelye

Department of Medical Biochemistry, Semmelweis University, Budapest, 1094, Hungary

Előadó telefonszáma

+36705377339

Előadó e-mail címe

sara.nazarian12@yahoo.com

Az előadás címe

MDH2 reducing oxaloacetate to malate provides NAD+ to KGDHC during respiratory arrest supporting glutaminolysis and mitochondrial substrate-level phosphorylation

Szerző(k) neve és munkahelye

Sara Nazarian1, Gergely Pallag1, Dora Ravasz1, David Bui1, Judit Doczi1, Krisztina Paal1, Noemi Karnok1, Samira Ait-El-Mkadem2, Veronique Paquis-Fluncklinger2, Christos Chinopoulos1
1Department of Medical Biochemistry, Semmelweis University, Budapest, 1094, Hungary
2Université Côte d’Azur, Inserm U1081, CNRS UMR7284, IRCAN, CHU de Nice, Nice, France

Bemutatás módja

Poszter

Szekció

Pharmaceutical Sciences - Posters E

Language of the presentation

English

Preferred session

Pharmaceutical Sciences

Összefoglaló szövege

Succinate-CoA ligase mediates mitochondrial substrate-level phosphorylation (mSLP) during which high-energy phosphates are generated in the absence of oxidative phosphorylation. For this, the provision of succinyl-CoA is necessary derived mostly from the preceding reaction catalyzed by KGDHC a critical enzyme for glutamine catabolism through the citric acid cycle. In turn, KGDHC depends on NAD+ the availability of which may be limited during respiratory arrest since the NADH-oxidizing function of complex I is impaired. Here, by using a host of bioenergetic and enzymatic analyses in cells from a patient suffering from MDH2 deficiency and mitochondria obtained from mouse tissues treated with the novel specific MDH2 inhibitor (E)-4-(((4,6-dimethylpyrimidin-2-yl)thio)methyl)-N'-(1-(4-methyl-3-nitrophenyl)ethylidene)benzohydrazide (CAS: 1013528-93-2) we show that MDH2 reducing oxaloacetate to malate during the respiratory arrest is a significant source of NAD+ for KGDHC. Through this, MDH2 sustains glutamine catabolism and mSLP in the absence of oxidative phosphorylation.

University and Doctoral School

Semmelweis University, János Szentágothai Doctoral School of Neurosciences

Other university and doctoral school, not listed above

Université Côte d’Azur, Inserm U1081, CNRS UMR7284, IRCAN, CHU de Nice, Nice, France

Supervisor

Dr. Christos Chinopolous

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

5054

Start

11:24

End

11:29

Authors (legacy)

Sara Nazarian1, Gergely Pallag1, Dora Ravasz1, David Bui1, Judit Doczi1, Krisztina Paal1, Noemi Karnok1, Samira Ait-El-Mkadem2, Veronique Paquis-Fluncklinger2, Christos Chinopoulos1
1Department of Medical Biochemistry, Semmelweis University, Budapest, 1094, Hungary
2Université Côte d’Azur, Inserm U1081, CNRS UMR7284, IRCAN, CHU de Nice, Nice, France