Tissue variation in the control of oxidative phosphorylation: Implication for mitochondrial diseases
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Metabolic control analysis has often been used for quantitative studies of the regulation of mitochondrial oxidative phosphorylations (OXPHOS). The main contribution of this work has been to show that the control of mitochondrial metabolic fluxes can be shared among several steps of the oxidative phosphorylation process, and that this distribution can vary according to the steady state and the tissue. However, these studies do not show whether this observed variation in the OXPHOS control is due to the experimental conditions or to the nature of the mitochondria. To find out if there actually exists a tissue variation in the distribution of OXPHOS control coefficients, we determined the control coefficients of seven OXPHOS complexes on the oxygen-consumption flux in rat mitochondria isolated from five different tissues under identical experimental conditions. Thus in this work, only the nature of the mitochondria can be responsible for any variation detected in the control coefficient values between different tissues. The analysis of control coefficient distribution shows two tissue groups: (i) the muscle and the heart, controlled essentially at the level of the respiratory chain; and (ii) the liver, the kidney and the brain, controlled mainly at the phosphorylation level by ATP synthase and the phosphate carrier. We propose that this variation in control coefficient according to the tissue origin of the mitochondria can explain part of the tissue specificity observed in mitochondrial cytopathies.
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Control experiments with atractyloside ensured that ADP/ATP exchange was mediated by the ADP/ATP carrier.
“Control experiments were carried out in the presence of atractyloside (ATR), a substrate of ANT, to ensure that the ADP/ATP exchange was mediated by the ADP/ATP carrier (Atlante et al., 2003; Rossignol et al., 2000; Wanders et al., 1984).”
From Mitochondrial Dysfunction Induced by Sertraline, an Antidepressant Agent (2012) · cites this paper as Rossignol et al., 2000
The Control coefficient determination and ANT control coefficients sections identify carboxyatractyloside (CATR) as an inhibitor used to study ANT. They do not report control experiments using atractyloside to establish that measured ADP/ATP exchange was mediated by the carrier; the measured flux was oxygen consumption. Page numbers are unavailable in our copy. (LLM, conf=0.85)
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- Authors
- ROSSIGNOL, R., LETELLIER, T., MALGAT, M., ROCHER, C., & MAZAT, J.-P.
- Affiliations
- Inserm (FR)
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2000-03-27
- Volume
- 347
- Issue
- 1
- Pages
- 45-53
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1220929
- OpenAlex
- W2093325321
- Cited by
- 202
- References
- 51
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 4 · 2017: 7 · 2016: 7 · 2015: 9 · 2014: 11 · 2013: 7 · 2012: 13
- FWCI
- 3.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- oxidative phosphorylation, metabolic control analysis, control coefficients, tissue variation, mitochondrial disease, oxygen consumption, ATP synthase, phosphate transporters, electron transport chain, muscle mitochondria, heart mitochondria, liver mitochondria, kidney mitochondria, brain mitochondria
- MeSH terms
- Animals, Antimycin A, Brain, Kidney, Kinetics, Male, Mitochondria, Mitochondria, Heart, Mitochondria, Liver, Mitochondria, Muscle, Organ Specificity, Oxidative Phosphorylation, Oxygen Consumption, Polarography, Rotenone, Rats, Wistar, Mitochondrial Myopathies, Rats
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