The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Low Reserve of Cytochrome c Oxidase Capacity in Vivo in the Respiratory Chain of a Variety of Human Cell Types
Open accessAbstract
The question of whether and to what extent the in vivo cytochrome c oxidase (COX) capacity in mammalian cells exceeds that required to support respiration is still unresolved. In the present work, to address this question, a newly developed approach for measuring the rate of COX activity, either as an isolated step or as a respiratory chain-integrated step, has been applied to a variety of human cell types, including several tumor-derived semidifferentiated cell lines, as well as specialized cells removed from the organism. KCN titration assays, carried out on intact uncoupled cells, have clearly shown that the COX capacity is in low excess (16-40%) with respect to that required to support the endogenous respiration rate. Furthermore, measurements of O2 consumption rate supported by 0.4 mM tetramethyl-p-phenylenediamine in antimycin-inhibited uncoupled intact cells have given results that are fully consistent with those obtained in the KCN titration experiments. Similarly, KCN titration assays on digitonin-permeabilized cells have revealed a COX capacity that is nearly limiting (7-22% excess) for ADP + glutamate/malate-dependent respiration. The present observations, therefore, substantiate the conclusion that the in vivo control of respiration by COX is much tighter than has been generally assumed on the basis of experiments carried out on isolated mitochondria. This conclusion has important implications for understanding the role of physiological or pathological factors in affecting the COX threshold.
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“It was initially characterized in diverse human cell lines, where COX activity was found to be higher than that required to support endogenous respiration rates, allowing this way some adaptability to higher respiratory needs (Villani et al, 1998).”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Villani et al, 1998
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Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302
Induction of Apoptotic Program in Cell-Free Extracts: Requirement for dATP and Cytochrome c
Liu, X., Kim, C. N., Yang, J., Jemmerson, R., & Wang, X. (1996) · Cell · doi:10.1016/s0092-8674(00)80085-9 · Cited by 5,167
Prevention of Apoptosis by Bcl-2: Release of Cytochrome c from Mitochondria Blocked
Yang, J., Liu, X., Bhalla, K. N., Kim, C. N., Ibrado, A. M., Cai, J., Peng, T.-I., Jones, D. P., & Wang, X. (1997) · Science · doi:10.1126/science.275.5303.1129 · Cited by 4,913
The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of Apoptosis
Kluck, R. M., Bossy‐Wetzel, E., Green, D. R., & Newmeyer, D. D. (1997) · Science · doi:10.1126/science.275.5303.1132 · Cited by 4,715
Close Contacts with the Endoplasmic Reticulum as Determinants of Mitochondrial Ca 2+ Responses
Rizzuto, R., Pinton, P., Carrington, W., Fay, F. S., Fogarty, K. E., Lifshitz, L. M., Tuft, R. A., & Pozzan, T. (1998) · Science · doi:10.1126/science.280.5370.1763 · Cited by 2,257
Human Cells Lacking mtDNA: Repopulation with Exogenous Mitochondria by Complementation
King, M. P., & Attardi, G. M. (1989) · Science · doi:10.1126/science.2814477 · Cited by 1,685
Self-citationHeinrich, R., & Rapoport, T. A. (1974) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1974.tb03318.x · Cited by 1,400
Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation
(1990) · Trends in Genetics · doi:10.1016/0168-9525(90)90040-d · Cited by 1,386
Diseases of the mitochondrial DNA
Wallace, D. C. (1992) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.61.070192.005523 · Cited by 1,319
Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line
Aden, D. P., Fogel, A., Plotkin, S. A., Damjanov, I., & Knowles, B. B. (1979) · Nature · doi:10.1038/282615a0 · Cited by 1,317
Research works printed but not linked: 1
- Biedler, 1973, Cancer Res., 33, 2643
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von Roretz, C., & Gallouzi, I. (2013) · Wiley-VCH eBooks · doi:10.1002/3527600906.mcb.201200012
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Oxygen toxicity and mitochondrial metabolism.
Li, J. (2003) · ThinkIR: The University of Louisville's Institutional Repository (University of Louisville) · doi:10.18297/etd/822
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Marrone, A., Geremia, E., Tomajoli, M. T. M., Marroccella, S. E., Petito, A., Fasciolo, G., Donnarumma, L., Venditti, P., Deidun, A., & Napolitano, G. (2026) · Marine Pollution Bulletin · doi:10.1016/j.marpolbul.2026.120224
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Metadata
- Authors
- Villani, G., Greco, M., Papa, S., & Attardi, G.
- Affiliations
- California Institute of Technology (US)
- University of Bari Aldo Moro (IT)
- Corresponding author
- Villani, Gaetano
- Attardi, Giuseppe
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1998-11
- Volume
- 273
- Issue
- 48
- Pages
- 31829-31836
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2109528024
- Cited by
- 225
- References
- 47
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 5 · 2023: 9 · 2022: 2 · 2021: 7 · 2020: 5 · 2019: 2 · 2018: 6 · 2017: 6 · 2016: 7 · 2015: 6 · 2014: 12 · 2013: 10 · 2012: 11
- FWCI
- 3.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (GM11726)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Keywords
- cytochrome c oxidase, electron transport chain, oxygen consumption, tetramethyl-p-phenylenediamine, digitonin-permeabilized cells, uncoupled respiration, cancer cell lines, human cell types
- MeSH terms
- Adenosine Diphosphate, Cell Differentiation, Cell Line, Cell Membrane Permeability, Electron Transport Complex IV, Digitonin, Carcinoma, Hepatocellular, Humans, Kinetics, Liver Neoplasms, Lung Neoplasms, Malates, Mitochondria, Multiple Myeloma, Neuroblastoma, Oxygen Consumption, Potassium Cyanide, Osteosarcoma, Tetramethylphenylenediamine, Tumor Cells, Cultured, Glutamic Acid
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