Cited by 225Mitochondrial Function and PathologyCancer and biochemical researchCoenzyme Q10 studies and effects

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Low Reserve of Cytochrome c Oxidase Capacity in Vivo in the Respiratory Chain of a Variety of Human Cell Types

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Villani, Gaetano, Greco, Marilena, Papa, Sergio, Attardi, Giuseppe·1998·Journal of Biological Chemistry

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Abstract

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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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
ORCID: Villani, Gaetano
Papa, Sergio
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)
DOI: 10.1074/jbc.273.48.31829
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: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 8011 d)
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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Low Reserve of Cytochrome c Oxidase Capacity in Vivo in the Respiratory Chain of a Variety of Human Cell Types

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