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Proline Oxidation Supports Mitochondrial ATP Production When Complex I Is Inhibited
- Source :
- International Journal of Molecular Sciences; Volume 23; Issue 9; Pages: 5111
- Publication Year :
- 2022
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2022.
-
Abstract
- 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 duroquinone fueling of CIII and CIV partially reproduced the effects of proline. Excess glutamate, 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.
- Subjects :
- Adenosine Triphosphatases
Electron Transport Complex I
Proline
proline dehydrogenase
substrate-level phosphorylation
coenzyme Q
reducing equivalent
Ubiquinone
Organic Chemistry
Glutamic Acid
General Medicine
Catalysis
Mitochondria
Computer Science Applications
Inorganic Chemistry
Mice
Adenosine Triphosphate
Proline Oxidase
Animals
Physical and Theoretical Chemistry
Molecular Biology
Spectroscopy
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences; Volume 23; Issue 9; Pages: 5111
- Accession number :
- edsair.doi.dedup.....f3e09676eb90c0a5691fe88f737fefe4
- Full Text :
- https://doi.org/10.3390/ijms23095111