MID51

MID51

Overview

```mermaid
flowchart TD
classDef gene fill:#0a1f0a,stroke:#4caf50
classDef protein fill:#0a1929,stroke:#2196f3
classDef disease fill:#2d0f0f,stroke:#e91e63
classDef pathway fill:#3e2200,stroke:#ff9800
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MID51["MID51"] -->|"implicated_in"| neurodegeneration["neurodegeneration"]
MID51["MID51"] -->|"interacts_with"| MID49["MID49"]
MID51["MID51"] -->|"interacts_with"| MFF["MFF"]
MID51["MID51"] -->|"regulates"| Aging["Aging"]
MID51["MID51"] -->|"interacts_with"| MIRO1["MIRO1"]
MID51["MID51"] -->|"regulates"| TOMM20["TOMM20"]
MID51["MID51"] -->|"associated_with"| FIS1["FIS1"]
MID51["MID51"] -->|"associated_with"| Parkinson["Parkinson"]
MID51["MID51"] -->|"associated_with"| Als["Als"]
MID51["MID51"] -->|"associated_with"| Mitophagy["Mitophagy"]
MID51["MID51"] -->|"regulates"| NEURODEGENERATIVE_DISEASES["NEURODEGENERATIVE DISEASES"]
MID51["MID51"] -->|"regulates"| MAX["MAX"]
MID51["MID51"] -->|"regulates"| AGING["AGING"]
MID51["MID51"] -->|"expressed_in"| T_Cell["T Cell"]
MID51["MID51"] -->|"interacts_with"| DRP1["DRP1"]
MID51["MID51"] -->|"associated_with"| MIRO1["MIRO1"]
DRP1["DRP1"] -->|"interacts_with"| MID51["MID51"]
TOMM20["TOMM20"] -->|"regulates"| MID51["MID51"]
MAX["MAX"] -->|"regulates"| MID51["MID51"]
MIRO1["MIRO1"] -->|"interacts_with"| MID51["MID51"]
MFF["MFF"] -->|"interacts_with"| MID51["MID51"]
MID49["MID49"] -->|"interacts_with"| MID51["MID51

MID51

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">MID51</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>MID51 (also MIEF1, SMCR7)</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Mitochondrial Dynamics Protein 51</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>22q13.31</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>54471</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000103184</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9NQC3</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/parkinson" style="color:#ef9a9a">Parkinson</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">27 edges</a></td>
</tr>
</table>

MID51 (Mitochondrial Dynamics Protein 51), also known as MIEF1 (Mitochondrial Elongation Factor 1), is a mitochondrial outer membrane protein that regulates mitochondrial fission. It plays a critical role in maintaining mitochondrial morphology and function, processes that are heavily implicated in neurodegenerative diseases. [@mid2023]

Gene Information

Function

MID51 is a key regulator of mitochondrial dynamics:

MID51 contains an N-terminal mitochondrial targeting sequence and a C-terminal external loop that interacts with DRP1. It exists in both monomeric and oligomeric forms.

Disease Associations

Parkinson's Disease

• MID51 variants are associated with PD susceptibility
• Mitochondrial dysfunction is a hallmark of PD pathogenesis
• MID51-mediated fission defects contribute to dopaminergic neuron vulnerability
• PINK1/PARKIN mitophagy pathway interacts with MID51 function

Alzheimer's Disease

• MID51 expression is altered in AD brain, particularly in affected regions
• Mitochondrial fission/fusion imbalance contributes to synaptic dysfunction
• [Amyloid-beta](/proteins/amyloid-beta) exposure disrupts MID51-mediated mitochondrial dynamics
• Therapeutic targeting of MID51 may protect against Aβ-induced mitochondrial damage

Amyotrophic Lateral Sclerosis (ALS)

• Mitochondrial fragmentation is observed in ALS models and patient tissue
• MID51 dysregulation contributes to motor neuron vulnerability
• Mutations in mitochondrial genes modify ALS progression

Huntington's Disease

• Mitochondrial dysfunction is central to HD pathogenesis
• Mutant [huntingtin](/proteins/huntingtin) interacts with MID51 and DRP1
• MID51 dysfunction may contribute to energy deficits in HD

optic atrophy

• MID51 mutations have been associated with autosomal dominant optic atrophy
• Demonstrates critical role in retinal ganglion cell survival

Expression

MID51 is expressed in:

• [Neurons](/entities/neurons): High expression in cortical neurons, hippocampal pyramidal cells, and dopaminergic neurons
• Retina: High expression in retinal ganglion cells
• Muscle: Moderate to high expression
• Heart: Moderate expression

Protein Structure and Mechanism

Structural Features

MID51 is a mitochondrial outer membrane protein with key structural elements:

• N-terminus: Mitochondrial targeting sequence
• Transmembrane domain: Single transmembrane helix anchoring to MOM
• C-terminus: Cytoplasmic domain interacting with DRP1
• Oligomerization domain: Forms higher-order structures

Molecular Mechanism

MID51 regulates mitochondrial fission through:

Post-translational Modifications

• Phosphorylation: Multiple sites regulate function
• Ubiquitination: Targets for degradation
• Sumoylation: Affects mitochondrial dynamics

Disease Mechanisms

Mitochondrial Dysfunction in AD

In Alzheimer's disease, MID51 function is altered:

• Altered expression: Changed levels in affected brain regions
• Fission imbalance: Excess fission or fusion defects
• Synaptic vulnerability: Mitochondrial deficits at synapses
• Aβ interaction: Direct effects of amyloid-beta

Dopaminergic Neuron Vulnerability in PD

MID51 contributes to PD through:

• Fission defects: Impaired mitochondrial division
• Mitophagy disruption: Altered quality control
• Energy deficits: Reduced ATP production
• Calcium handling: Impaired calcium homeostasis

Optic Atrophy

MID51 mutations affect retinal ganglion cells:

• Cellular specificity: High mitochondrial demand
• Axonal transport: Long axonal projections
• Energy failure: Insufficient ATP for function

Therapeutic Strategies

Small Molecule Approaches

Gene Therapy

• MID51 overexpression: Restore fission capacity
• Variant correction: Correct pathogenic variants
• Cell-type specific: Targeted delivery

Neuroprotection

• Combination therapies: Multi-target approaches
• Adjunctive treatments: Enhance current therapies
• Preventive strategies: Early intervention

Biomarker Potential

Diagnostic Applications

• Blood biomarkers: Peripheral indicators
• Imaging markers: Mitochondrial function
• Disease progression: Severity correlates

Animal Models

Knockout Studies

• MID51 knockout: Embryonic lethal in mice
• Conditional knockout: Tissue-specific effects
• Phenotypes: Mitochondrial abnormalities

Transgenic Models

• Overexpression: Protected neurons
• Mutant models: Disease simulation
• Rescue studies: Therapeutic testing

Key Publications

Therapeutic Implications

• Mitochondrial Modulators: Small molecules targeting MID51-DRP1 interaction may improve mitochondrial function
• Neuroprotective Strategies: MID51 enhancement may protect vulnerable neuronal populations
• Combination Therapy: Mitochondrial-targeting approaches may complement other disease-modifying strategies

See Also

• [Mitochondrial Dynamics in Neurodegeneration](/mechanisms/mitochondrial-dynamics-neurodegeneration)
• [DRP1](/genes/drp1)
• [Mitochondrial Dysfunction](/mechanisms/mitochondrial-dysfunction)
• [Mitophagy in Neurodegeneration](/mechanisms/mitophagy-neurodegeneration)
• [PINK1](/genes/pink1)
• [PARK7](/genes/park7)
• [MFN2](/genes/mfn2)
• [OPA1](/genes/opa1)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving MID51 discovered through SciDEX knowledge graph analysis: