Role of calcium ions in the regulation of intramitochondrial metabolism. Properties of the Ca2+-sensitive dehydrogenases within intact uncoupled mitochondria from the white and brown adipose tissue of the rat
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1. Increasing concentrations of both Ca2+ and Sr2+ (generated by using EGTA buffers) resulted in 4-fold increases in the initial activity of pyruvate dehydrogenase within intact uncoupled mitochondria from rat epididymal adipose tissue incubated in the presence of the ionophore A23187, ATP, Mg2+ and oligomycin. The k0.5 values (concentrations required for half-maximal effects) for Ca2+ and Sr2+ were 0.54 and 7.1 microM respectively. In extracts of the mitochondria, pyruvate dehydrogenase phosphate phosphatase activity was stimulated about 4-fold by Ca2+ and Sr2+, with k0.5 values of 1.08 and 6.4 microM respectively. 2. NAD+-isocitrate dehydrogenase and oxoglutarate dehydrogenase appeared to be rate-limiting in the oxidation of threo-Ds-isocitrate and oxoglutarate by uncoupled mitochondria from brown adipose tissue of cold-adapted rats. Ca2+ (and Sr2+) diminished the Km for the oxidation of both threo-Ds-isocitrate and oxoglutarate. The kinetic constants for these oxidations were very similar to those obtained for the activities of NAD+-isocitrate dehydrogenase and oxoglutarate dehydrogenase in extracts of the mitochondria. In particular, the k0.5 values for Ca2+ were all in the range 0.2–1.6 microM and Sr2+ was found to mimic Ca2+, but with k0.5 values about 10 times greater. 3. Overall, the results of this study demonstrate that the activities of pyruvate dehydrogenase, NAD+-isocitrate dehydrogenase and oxoglutarate dehydrogenase may all be increased by Ca2+ and Sr2+ within intact mitochondria. In all cases the k0.5 values are close to 1 and 10 microM respectively, as found for the separated enzymes. Experiments on brown-adipose-tissue mitochondria incubated in the presence of albumin suggest that it may be possible to use the sensitivity of the dehydrogenases to Ca2+ as a means of assessing the distribution of Ca2+ across the mitochondrial inner membrane.
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Support for a role of ROS in HIF-1α stabilization derives from studies showing that the absence of cytochrome c or blocked Rieske Fe-S proteins under hypoxic conditions blocks HIF-1α stabilization.
“Support for a role of ROS in HIF-1α stabilization derives from studies showing that the absence of cytochrome c or blocked Rieske Fe-S proteins under hypoxic conditions blocks HIF-1α stabilization (61, 221).”
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Self-citationMcCormack, J. G., Bromidge, E. S., & Dawes, N. J. (1988) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(88)90088-6 · Cited by 27 · see citing works
Self-citationCarvalho, A. P. (1982) · Springer eBooks · doi:10.1007/978-1-4757-0614-7_3 · Cited by 27 · see citing works
Pyruvate utilization by synaptosomes is independent of calcium
Kauppinen, R. A., & Nicholls, D. G. (1986) · FEBS Letters · doi:10.1016/0014-5793(86)80484-7 · Cited by 26 · see citing works
THE MECHANISM OF α‐ADRENERGIC AGONIST ACTION IN LIVER
Reinhart, P. H., Taylor, W. M., & Bygrave, F. L. (1984) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/j.1469-185x.1984.tb00413.x · Cited by 24 · see citing works
Haumann, J., Camara, A. K. S., Gadicherla, A. K., Navarro, C. D., Boelens, A. D., Blomeyer, C. A., Dash, R. K., Boswell, M. R., Kwok, W., & Stowe, D. F. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2018.01914 · Cited by 23 · see citing works
Gao, X., Di, X., Li, J., Kang, Y., Xie, W., Sun, L., & Zhang, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054991 · Cited by 23 · see citing works
- Authors
- McCormack, J. G., & Denton, R. M.
- Affiliations
- University of Bristol (GB)
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 1980-07-15
- Volume
- 190
- Issue
- 1
- Pages
- 95-105
- ISSN
- 0264-6021 (ISSN-L)
- PMC
- PMC1162067
- OpenAlex
- W130501137
- Cited by
- 165
- References
- 17
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 2 · 2019: 2 · 2018: 5 · 2017: 3 · 2016: 1 · 2015: 2 · 2013: 4 · 2012: 3
- FWCI
- 5.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- calcium ions, pyruvate dehydrogenase, NAD-isocitrate dehydrogenase, 2-oxoglutarate dehydrogenase, strontium, white adipose tissue, brown adipose tissue, cold adaptation, substrate Km, A23187
- MeSH terms
- Calcimycin, Adenosine Triphosphate, Adipose Tissue, Animals, Adipose Tissue, Brown, Calcium, Kinetics, Male, Mitochondria, Oxidoreductases, Serum Albumin, Bovine, Strontium, Rats, In Vitro Techniques
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