OPA1 Protein

OPA1 Protein

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">OPA1 Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>OPA1 (Dynamin-like 120kDa)</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>OPA1</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>O60393</td>
</tr>
<tr>
<td class="label">PDB Structure</td>
<td>5W5V, 6JTG</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~100 kDa (isoforms 83-100 kDa)</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Mitochondrial inner membrane</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Dynamin GTPase family</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Status</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Small molecule activators</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Mitochondrial protectants</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">421 edges</a></td>
</tr>
</table>

...

OPA1 Protein

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">OPA1 Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>OPA1 (Dynamin-like 120kDa)</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>OPA1</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>O60393</td>
</tr>
<tr>
<td class="label">PDB Structure</td>
<td>5W5V, 6JTG</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~100 kDa (isoforms 83-100 kDa)</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Mitochondrial inner membrane</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Dynamin GTPase family</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Status</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Small molecule activators</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Mitochondrial protectants</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">421 edges</a></td>
</tr>
</table>

Introduction

Opa1 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

This page provides comprehensive information about OPA1 Protein, including its structure, normal function in the nervous system, and its role in neurodegenerative diseases. [@ferre2015]

OPA1 (Optic Atrophy 1 protein) is a dynamin-related GTPase localized to the mitochondrial inner membrane where it mediates inner membrane fusion and maintains cristae structure. It is essential for mitochondrial function and neuronal survival. [@carelli2015]

Basic Information

Structure

OPA1 contains multiple functional domains:

• N-terminal GTPase domain: Catalyzes GTP hydrolysis for membrane fusion
• Middle domain: Involved in protein-protein interactions
• GTPase effector domain (GED): Regulates GTPase activity
• C-terminal transmembrane region: Anchors protein to inner membrane

OPA1 undergoes proteolytic processing generating long (L-OPA1) and short (S-OPA1) isoforms with distinct functions.

Normal Function

In the nervous system, OPA1 maintains:

• Mitochondrial network connectivity: Inner membrane fusion maintains tubular network
• Cristae structure: OPA1 preserves cristae curvature and cytochrome c stores
• Respiratory function: Proper cristae support efficient OXPHOS
• Calcium buffering: Mitochondrial calcium uptake and release
• Apoptotic regulation: OPA1 cleavage releases cytochrome c during [apoptosis](/entities/apoptosis)
• mtDNA maintenance: OPA1 is required for mitochondrial DNA nucleoid organization

Role in Disease

Alzheimer's Disease

• OPA1 expression reduced in AD brain
• Mitochondrial fragmentation observed in AD [neurons](/entities/neurons)
• OPA1 dysfunction contributes to bioenergetic deficits
• Therapeutic target: OPA1 agonists under investigation

Parkinson's Disease

• OPA1 deficiency sensitizes dopaminergic neurons to mitochondrial toxins
• OPA1 polymorphisms associated with PD risk
• Mitochondrial fragmentation in PD models

Amyotrophic Lateral Sclerosis (ALS)

• OPA1 aggregates detected in ALS motor neurons
• OPA1 dysfunction contributes to mitochondrial dysfunction
• Energy deficits in ALS

Autosomal Dominant Optic Atrophy (ADOA)

• Heterozygous OPA1 mutations cause haploinsufficiency
• Retinal ganglion cell death leads to progressive vision loss
• Most common inherited optic neuropathy

Therapeutic Targeting

Key Publications

Yu-Wai-Man P, et al. (2010) OPA1 mutations induce mitochondrial DNA instability. Brain. 133(Pt 3):771-784.

Delettre C, et al. (2000) Nuclear gene OPA1, encoding a dynamin-related GTPase, is mutated in dominant optic atrophy. Nat Genet. 26(2):207-210.

Carelli V, et al. (2015) Motor neuron disease resulting from inheritance of a pathogenic OPA1 variant. Neurology. 85(9):786-789.

Animal Models

Several animal models have been developed to study OPA1 dysfunction:

• Opa1+/- mice: Heterozygous knockout mice exhibit mitochondrial fragmentation and age-related retinal degeneration, mimicking human ADOA
• Opa1 conditional knockout: Neuron-specific deletion causes progressive neurodegeneration and motor deficits
• Drosophila OPA1: Fruit fly models show mitochondrial fragmentation and lifespan reduction
• Zebrafish opa1: Morpholino knockdowns demonstrate developmental defects and mitochondrial abnormalities

Biomarkers

OPA1 dysfunction can be assessed through several biomarkers:

• Serum OPA1 levels: Reduced circulating OPA1 correlates with disease severity in AD and PD
• Mitochondrial fragmentation index: Peripheral blood mononuclear cell analysis shows increased fission
• Optical coherence tomography (OCT): Retinal nerve fiber layer thinning in OPA1 mutation carriers
• Muscle biopsy: Mitochondrial structural abnormalities visible via electron microscopy

Research Directions

Current research focuses on:

• Development of OPA1-specific agonists and gene therapy vectors
• Understanding the relationship between OPA1 processing and neuronal survival
• Identifying modifiers of OPA1 mutation penetrance
• Exploring mitochondrial dynamics as a therapeutic target in neurodegeneration

Background

The study of Opa1 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

References

^{[[1]](https://pubmed.ncbi.nlm.nih.gov/15776380/)} OPA1 and mitochondrial function. PMID: 15776380(https://pubmed.ncbi.nlm.nih.gov/15776380/)

See Also

• OPA1 Gene
• [Mitochondrial Dysfunction Pathway](/mechanisms/mitochondrial-dysfunction)
• [MFN2 Protein](/proteins/mfn2-protein)
• [DRP1 Protein](/proteins/drp1-protein)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [UniProt: OPA1](https://www.uniprot.org/uniprot/O60393)
• [PDB: OPA1](https://www.rcsb.org/structure/5W5V)
• [NCBI Protein: OPA1](https://www.ncbi.nlm.nih.gov/protein/O60393)