Suppression mechanisms of COX assembly defects in yeast and human: Insights into the COX assembly process
Open accessAbstract
Eukaryotic cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain. COX is a multimeric enzyme formed by subunits of dual genetic origin whose assembly is intricate and highly regulated. In addition to the structural subunits, a large number of accessory factors are required to build the holoenzyme. The function of these factors is required in all stages of the assembly process. They are relevant to human health because devastating human disorders have been associated with mutations in nuclear genes encoding conserved COX assembly factors. The study of yeast strains and human cell lines from patients carrying mutations in structural subunits and COX assembly factors has been invaluable to attain the current state of knowledge, even if still fragmentary, of the COX assembly process. After the identification of the genes involved, the isolation and characterization of genetic and metabolic suppressors of COX assembly defects, reviewed here, have become a profitable strategy to gain insight into their functions and the pathways in which they operate. Additionally, they have the potential to provide useful information for devising therapeutic approaches to combat human disorders associated with COX deficiency.
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COX1 depletion results in defective assembly, and delivery of nuclear-encoded subunits reduces COX1 levels and also disrupts assembly.
“COX1 depletion results in defective assembly, and delivery of nuclear-encoded subunits reduces COX1 levels and also disrupts assembly [82–87].”
From Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function (2019) · cites this paper as [87]
Section 2.4 reports that Cox1p synthesis is down-regulated in yeast when its assembly partners are absent, and that reduced Cox1p synthesis accompanies failed COX assembly. It does not say that delivery of nuclear-encoded subunits reduces COX1 levels; the reported relationship concerns the absence of assembly partners, not their delivery. (LLM, conf=0.85)
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- Authors
- Barrientos, A., Gouget, K., Horn, D., Soto, I. C., & Fontanesi, F.
- Affiliations
- University of Miami (US)
- Corresponding author
- Barrientos, Antoni
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 1793
- Issue
- 1
- Pages
- 97-107
- ISSN
- 0167-4889 (ISSN-L)
- PMC
- PMC2644423
- OpenAlex
- W2123634642
- Cited by
- 99
- References
- 6
- Citations by year
- 2026: 1 · 2024: 2 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 6 · 2016: 1 · 2015: 6 · 2014: 4 · 2013: 10 · 2012: 13
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Muscular Dystrophy Association
- National Institutes of Health
- National Institute of General Medical Sciences (GM-071775A, R01GM071775)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- cytochrome c oxidase, genetic suppressors, assembly factors, mitochondrial respiratory chain, yeast model, human disorders, treatment options
- MeSH terms
- Animals, Electron Transport Complex IV, Heme, Humans, Mammals, Models, Biological, Saccharomyces cerevisiae, Cytochrome-c Oxidase Deficiency
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