Pallag 2022 Abstract Bioblast

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P06.
Pallag Gergely
Pallag Gergely, Nazarian S, Ravasz D, Bui D, Komlódi T, Doerrier C, Gnaiger E, Seyfried TN, Chinopoulos C (2022) Proline oxidation supports mitochondrial ATP production when Complex I is inhibited.
Bioblast 2022: BEC Inaugural Conference. In: https://doi.org/10.26124/bec:2022-0001
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Link: Bioblast 2022: BEC Inaugural Conference

Pallag Gergely, Nazarian Sara, Ravasz Dora, Bui David, Komlodi Timea, Doerrier Carolina, Gnaiger Erich, Seyfried Thomas N, Chinopoulos Christos (2022)

Event: Bioblast 2022

The oxidation of proline to pyrroline-5-carboxylate (P5C) leads to the transfer of electrons to ubiquinone in mitochondria that express proline dehydrogenase (ProDH). This electron transfer supports Complexes CIII and CIV, thus generating the protonmotive force. Further catabolism of P5C forms glutamate, which fuels the citric acid cycle that yields the reducing equivalents that sustain oxidative phosphorylation. However, P5C and glutamate catabolism depend on CI activity due to NAD+ requirements.

NextGen-O2k (Oroboros Instruments) was used to measure proline oxidation in isolated mitochondria of various mouse tissues. Simultaneous measurements of oxygen consumption, membrane potential, NADH, and the ubiquinone redox state were correlated to ProDH activity and F1FO-ATPase directionality.

Proline catabolism generated a sufficiently high membrane potential that was able to maintain the F1FO-ATPase operation in the forward mode. This was observed in CI-inhibited mouse liver and kidney mitochondria that exhibited high levels of proline oxidation and ProDH activity. This action was not observed under anoxia or when either CIII or CIV were inhibited. The duroquinol fueling of CIII and CIV partially reproduced the effects of proline. Excess glutamate in the presence of malate, however, could not reproduce the proline effect, suggesting that processes upstream of the glutamate conversion from proline were involved. The ProDH inhibitors tetrahydro-2-furoic acid and, to a lesser extent, S-5-oxo-2-tetrahydrofurancarboxylic acid abolished all proline effects.

The data show that ProDH-directed proline catabolism could generate sufficient CIII and CIV proton pumping, thus supporting ATP production by the F1FO-ATPase even under CI inhibition [1].

  1. Pallag G, Nazarian S, Ravasz D, Bui D, Komlódi T, Doerrier C, Gnaiger E, Seyfried TN, Chinopoulos C (2022) Proline oxidation supports mitochondrial ATP production when Complex I is inhibited. https://doi.org/10.3390/ijms23095111

Keywords: proline dehydrogenase; substrate-level phosphorylation; coenzyme Q; reducing equivalent

O2k-Network Lab: AT Innsbruck Oroboros, HU Budapest Chinopoulos C, HU Budapest Tretter L


Affiliations and support

Pallag G1, Nazarian S1, Ravasz D1, Bui D1, Komlódi T2, Doerrier C2, Gnaiger E2, Seyfried TN3, Chinopoulos C1
  1. Dept of Biochemistry and Molecular Biology, Semmelweis Univ., 1094 Budapest, Hungary - [email protected]
  2. Oroboros Instruments, 6020 Innsbruck, Austria
  3. Biology Dept, Boston College, Chestnut Hill, MA 02467, USA
Template NextGen-O2k.jpg
This work was supported by grants from NKFIH ([TKP2021-EGA-25], FIKP-61822-64888-EATV, VEKOP 2.3.3-15-2016-00012, 2017-2.3.4-TET-RU-2017-00003, KH129567, and K135027) to C.C. and from the project NextGen-O2k (Oroboros Instruments) which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 859770.

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