COX4I1 Protein — Cytochrome C Oxidase Subunit 4I1

COX4I1 Protein — Cytochrome C Oxidase Subunit 4I1

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">COX4I1 Protein — Cytochrome C Oxidase Subunit 4I1</th>
</tr>
<tr>
<td class="label">Gene</td>
<td>[COX4I1](/genes/cox4i1)</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P12074" target="_blank">P12074</a></td>
</tr>
<tr>
<td class="label">PDB</td>
<td><a href="https://www.rcsb.org/structure/5ZVA" target="_blank">5ZVA</a></td>
</tr>
<tr>
<td class="label">Mol.

COX4I1 Protein — Cytochrome C Oxidase Subunit 4I1

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">COX4I1 Protein — Cytochrome C Oxidase Subunit 4I1</th>
</tr>
<tr>
<td class="label">Gene</td>
<td>[COX4I1](/genes/cox4i1)</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P12074" target="_blank">P12074</a></td>
</tr>
<tr>
<td class="label">PDB</td>
<td><a href="https://www.rcsb.org/structure/5ZVA" target="_blank">5ZVA</a></td>
</tr>
<tr>
<td class="label">Mol. Weight</td>
<td>17 kDa</td>
</tr>
<tr>
<td class="label">Localization</td>
<td>Mitochondrial inner membrane (Complex IV)</td>
</tr>
<tr>
<td class="label">Family</td>
<td>Cytochrome c oxidase subunit IV family</td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Alzheimer's Disease](/diseases/alzheimers), [Parkinson's Disease](/diseases/parkinsons-disease), [COX Deficiency](/diseases/neurons)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cardiovascular" style="color:#ef9a9a">Cardiovascular</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a>, <a href="/wiki/ischemia" style="color:#ef9a9a">Ischemia</a></td>
</tr>
<tr>
<td class="label">SciDEX Hypotheses</td>
<td><a href="/hypothesis/h-fd1562a3" style="color:#ce93d8" title="Score: 0.47">Near-infrared light therapy stimulates C...</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">156 edges</a></td>
</tr>
</table>

COX4I1 Protein — Cytochrome C Oxidase Subunit 4I1

Introduction

[COX4I1](/genes/cox4i1) encodes cytochrome c oxidase subunit IV isoform 1, a key regulatory subunit of Complex IV in the mitochondrial electron transport chain[@nature2010]. This protein plays a crucial role in oxidative phosphorylation and cellular energy production, with well-documented dysfunction in neurodegenerative diseases including [Alzheimer's Disease](/diseases/alzheimers-disease) and [Parkinson's Disease](/diseases/parkinsons-disease)[@dimauro2003].

Overview

COX4I1 is one of two isoforms of cytochrome c oxidase subunit IV (COX4I1 and COX4I2). COX4I1 is the dominant isoform in most tissues, including the brain, and is regulated by oxygen levels and metabolic demand[@lin2006].

Cytochrome c oxidase (Complex IV) is the terminal enzyme of the electron transport chain:

• Pumps protons from matrix to intermembrane space
• Transfers electrons to oxygen to form water
• Composed of 13 subunits (3 catalytic, 10 structural)

Structure

COX4I1 features:

• Two transmembrane helices
• Large intermembrane space domain
• Molecular weight approximately 17 kDa
• Binds heme a and copper centers

Normal Function

Electron Transport Chain

• Terminal electron acceptor in ETC
• Couples electron transfer to proton pumping
• Essential for ATP synthesis

Regulation

• Regulated by oxygen availability (via HIF-1)
• Subject to retrograde signaling from mitochondria
• Assembly assisted by COX chaperones

Tissue-Specific Expression

In [neurons](/entities/neurons):

• High expression in high-energy requiring regions
• Important for synaptic function
• Supports axonal mitochondrial trafficking

Role in Disease

Alzheimer's Disease

• Reduced COX4I1 expression in AD brains
• Contributes to hippocampal dysfunction
• Linked to [amyloid-beta](/proteins/amyloid-beta) and [tau](/proteins/tau) pathology
• Results in oxidative stress

Parkinson's Disease

• Complex IV deficiency in substantia nigra
• Contributes to dopaminergic neuron loss
• Linked to complex I interactions
• May affect [alpha-synuclein](/proteins/alpha-synuclein) toxicity

COX Deficiency

• Leigh syndrome and other mitochondrial disorders
• Severe neurological deficits
• lactic acidosis

Key Publications

See Also

• [Mitochondrial Dynamics](/mechanisms/mitochondrial-dynamics)
• [Electron Transport Chain](/mechanisms/electron-transport-chain)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [UniProt: cox4i1](https://www.uniprot.org/)
• [PubMed: cox4i1](https://pubmed.ncbi.nlm.nih.gov/?term=cox4i1+neurodegeneration)

References