[@kadenbach2000]
[@liu2019]
[@wang2018]
[@gorman2016]
[@zeighami2019]
[@schapira2019]
| Cytochrome c Oxidase Subunit VIc |
|---|
| Gene Symbol | COX6C |
| Full Name | Cytochrome c Oxidase Subunit VIc |
| Chromosomal Location | 8q22.2 |
| NCBI Gene ID | 10455 |
| OMIM | 615124 |
| Ensembl ID | ENSG00000164930 |
| UniProt ID | COX6C_HUMAN |
| Associated Diseases | [Parkinson's Disease](/diseases/parkinsons-disease) [Alzheimer's Disease](/diseases/alzheimers-disease) [Leigh Syndrome](/diseases/leigh-syndrome) |
COX6C is a human gene whose product cOX6C** encodes cytochrome c oxidase subunit VIc, a nuclear-encoded subunit of mitochondrial complex IV (cytochrome c oxidase). This is the terminal enzyme of the electron transport chain, responsible for reducing oxygen to water and pumping protons across the inner mitochondrial membrane 1. Variants in COX6C have been implicated in Parkinson's Disease, Alzheimer's Disease, Leigh Syndrome. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
COX6C encodes cytochrome c oxidase subunit VIc, a nuclear-encoded subunit of mitochondrial complex IV (cytochrome c oxidase). This is the terminal enzyme of the electron transport chain, responsible for reducing oxygen to water and pumping protons across the inner mitochondrial membrane 1.
COX6C is a small hydrophobic protein that contributes to the structural stability of the complex. While not directly involved in catalysis, it plays an important role in maintaining proper complex assembly and function 2.
- Part of complex IV (cytochrome c oxidase)
- Contributes to proton gradient generation
- Essential for oxygen consumption in neurons
- Regulated by neuronal activity 3
COX6C and other complex IV subunits show altered expression in PD brain. Complex IV deficiency leads to impaired energy production and increased oxidative stress in dopaminergic neurons 4.
Complex IV dysfunction is prominent in AD, with COX6C expression downregulated in affected brain regions. This contributes to the hypometabolism observed in AD patients 5.
Pathogenic variants in complex IV subunits can cause Leigh syndrome, characterized by progressive neurological decline and bilateral brain lesions 6.
COX6C is expressed throughout the brain:
- Cerebral cortex - high in pyramidal neurons
- Hippocampus - CA1 region particularly affected
- Substantia nigra - dopaminergic neurons
- Cerebellum - Purkinje cells
Neuronal activity can modulate COX6C expression, linking energy metabolism to neural function 8.
- Coenzyme Q10 may improve electron transport
- Dichloroacetate targets mitochondrial dysfunction
- PGC-1α agonists promote mitochondrial biogenesis 9
- Richter et al., Complex IV (2019)
- Kahle et al., Mitochondria (2019)
- Unknown, Kadenbach, Complex IV regulation (2000)
- Liu et al., PD (2019)
- Wang et al., AD (2018)
- Gorman et al., Leigh (2016)
- Zeighami et al., Expression (2019)
- Unknown, Schapira, Therapy (2019)
- Barrett et al., Mitochondrial cytochrome c oxidase deficiency (2015)
- Johnson et al., Cytochrome c oxidase deficiency (2018)
- Sai et al., alpha-Synuclein induced mitochondrial dysfunction via cytochrome c oxidase subunit 2 in SH-SY5Y cells (2019)
- Sink et al., The subunit composition and function of mammalian cytochrome c oxidase (2016)
- Villani et al., Mitochondrial respiration is controlled by Allostery, Subunit Composition and Phosphorylation Sites of Cytochrome c Oxidase (2019)
- Huttemann et al., Deciphering the role of mitochondrial cytochrome C oxidase subunit 4 in cardiac health and disease (2023)
- Balsa et al., NDUFA4 (Renamed COXFA4) Is a Cytochrome-c Oxidase Subunit (2017)
- Lee et al., Cytochrome c oxidase dysfunction in oxidative stress (2012)
- Giachin et al., Cytochrome c oxidase deficiency (2016)
- Masaoka et al., Role of nuclear-encoded subunit Vb in the assembly and stability of cytochrome c oxidase complex (2003)
- Arnold S et al., Cytochrome c oxidase and its role in neurodegeneration and neuroprotection (2012)
- León J et al., Melatonin mitigates mitochondrial malfunction (2005)
- Musatov A & Robinson NC, Susceptibility of mitochondrial electron-transport complexes to oxidative damage (2012)
- Jomova K et al., Metals, oxidative stress and neurodegenerative disorders (2010)
- Novack GV et al., Mitochondrial Supercomplexes: Physiological Organization and Dysregulation in Age-Related Neurodegenerative Disorders (2020)