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mdm31

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">mdm31</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>MDM31</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Mitochondrial Dynamics Protein Mdm31</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>5p15.2</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>166785</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000132906</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q8N5M4</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>438 amino acids</td>
</tr>
<tr>
<td class="label">Subcellular Location</td>
<td>Mitochondrial inner membrane</td>
</tr>
<tr>
<td class="label">Tissue</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Brain</td>
<td>Very High</td>
</tr>
<tr>
<td class="label">Heart</td>
<td>Very High</td>
</tr>
<tr>
<td class="label">Skeletal Muscle</td>
<td>High</td>
</tr>
<tr>
<td class="label">Liver</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Kidney</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

...

mdm31

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">mdm31</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>MDM31</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Mitochondrial Dynamics Protein Mdm31</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>5p15.2</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>166785</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000132906</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q8N5M4</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>438 amino acids</td>
</tr>
<tr>
<td class="label">Subcellular Location</td>
<td>Mitochondrial inner membrane</td>
</tr>
<tr>
<td class="label">Tissue</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Brain</td>
<td>Very High</td>
</tr>
<tr>
<td class="label">Heart</td>
<td>Very High</td>
</tr>
<tr>
<td class="label">Skeletal Muscle</td>
<td>High</td>
</tr>
<tr>
<td class="label">Liver</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Kidney</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

MDM31 (Mitochondrial Dynamics Protein Mdm31) is a nuclear-encoded mitochondrial inner membrane protein that plays critical roles in mitochondrial morphology regulation, cristae organization, and mitochondrial DNA (mtDNA) maintenance. Located on chromosome 5p15.2, this gene encodes a 438-amino acid protein that is essential for proper mitochondrial function in high-energy-demanding tissues, particularly the brain[@merrill2011].

Mermaid diagram (expand to render)

Mitochondrial dynamics—the balance between mitochondrial fission and fusion—is essential for neuronal survival. MDM31 is a key player in these processes, specifically regulating inner membrane dynamics that affect cristae structure, mtDNA distribution, and metabolic function. Dysregulation of these processes contributes to the pathogenesis of Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions["@duboff2015"]. Located on chromosome 5p15.2, this gene encodes a 438-amino acid protein that is essential for proper mitochondrial function in high-energy-demanding tissues, particularly the brain["@merrill2011"].

Mitochondrial dynamics—the balance between mitochondrial fission and fusion—is essential for neuronal survival. MDM31 is a key player in these processes, specifically regulating inner membrane dynamics that affect cristae structure, mtDNA distribution, and metabolic function. Dysregulation of these processes contributes to the pathogenesis of Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions["@duboff2015"].

Structural Biology

Protein Domains

MDM31 comprises several functional domains[@kuwahara2018]:

N-terminal matrix domain (1-150 aa):

Enzimatic activity
ATP binding site
OPA1 interaction interface
Conformational changes upon activation

Transmembrane helix (150-180 aa):

Single-pass membrane anchor
Critical for inner membrane localization
Forms dimerization interface

C-terminal regulatory domain (180-438 aa):

Protein-protein interactions
Regulatory modification sites

-mtDNA nucleoid binding

Structural Insights

Homology models suggest:

Coiled-coil regions for oligomerization
Flexible linker regions
Dimerization-driven function

Oligomerization

MDM31 functions as oligomers:

Dimeric structure
Higher-order assemblies
Dynamic regulation

Gene Overview

Protein Structure and Function

Structural Features

MDM31 has a characteristic mitochondrial inner membrane protein architecture:

N-terminal domain (1-150 aa): Matrix-facing domain with enzymatic activity
Transmembrane domain (150-180 aa): Single transmembrane helix anchoring protein in inner membrane
C-terminal domain (180-438 aa): Intermembrane space-facing domain with regulatory functions
Coiled-coil regions: Involved in protein-protein interactions

The protein localizes to the mitochondrial inner membrane with a single transmembrane domain that anchors it while allowing both N- and C-terminal domains to face the matrix space. This orientation enables MDM31 to interact with both matrix proteins and inner membrane components[@kuwahara2018].

Functions in Mitochondrial Biology

Mitochondrial Morphology Regulation

MDM31 is a crucial component of the mitochondrial fission machinery:

Inner membrane fission: Partners with OPA1 for inner membrane scission
Cristae remodeling: Controls cristae junction formation and maintenance
Nucleoid distribution: Regulates mtDNA nucleoid positioning and segregation

Mitochondrial DNA Maintenance

MDM31 plays essential roles in mtDNA maintenance:

Nucleoid organization: Controls distribution and copy number of mtDNA
Replication machinery: Interacts with DNA polymerase γ and other replisome components
mtDNA integrity: Protects against mtDNA mutations and deletions

Cristae Organization

Proper cristae structure is essential for oxidative phosphorylation:

Cristae junctions: MDM31 regulates the formation and maintenance of cristae junctions
ATP synthase organization: Cristae geometry affects ATP synthase dimerization and function
Respiratory chain assembly: Proper cristae structure supports respiratory complex assembly[@yang2020]

Interaction Network

MDM31 interacts with several key mitochondrial proteins[@petersen2022]:

OPA1: Inner membrane fusion and cristae organization
MTORC1: Metabolic regulation
DNA polymerase γ: mtDNA replication
ATP synthase subunits: Metabolic coupling
DRP1: Fission coordination
Mitofusins: Outer membrane dynamics
TIMM proteins: Protein import

MDM31 Interaction Map

Mermaid diagram (expand to render)

Disease Associations

Alzheimer's Disease

Mitochondrial dysfunction is a central feature of AD pathogenesis, and MDM31 contributes to several aspects:

Bioenergetic Failure

Mitochondrial cristae alterations: Reduced cristae density in AD neurons
ATP production deficits: Impaired oxidative phosphorylation
Metabolic inflexibility: Inability to meet energy demands[@wang2011]

Amyloid-Beta Effects

Aβ accumulates in mitochondria and directly impairs mitochondrial dynamics
MDM31 dysfunction compounds amyloid-induced mitochondrial damage
Creates feed-forward cycle of bioenergetic failure

Tau Pathology

Hyperphosphorylated tau disrupts mitochondrial transport
Alters MDM31 distribution in neurons
Impairs local energy supply at synapses[@reddy2011]

Mitochondrial DNA Damage

Increased mtDNA mutations in AD brain
MDM31 deficiency exacerbates mtDNA damage accumulation
Affects mitochondrial gene expression

Parkinson's Disease

Dopaminergic neurons are particularly vulnerable to mitochondrial dysfunction:

PINK1/Parkin Pathway

MDM31 may interact with PINK1/Parkin-mediated mitophagy
Mitochondrial dynamics defects impair quality control
Contributes to dopaminergic neuron loss[@iijima2020]

Alpha-Synuclein Mitochondrial Binding

α-syn localizes to mitochondria in PD models
MDM31 dysfunction affects α-syn handling
Contributes to mitochondrial dysfunction

Neuroinflammation

Mitochondrial dysfunction activates inflammatory pathways
MDM31 deficiency promotes microglial activation
Contributes to neuroinflammatory cascade

Other Neurodegenerative Conditions

Charcot-Marie-Tooth Disease

MDM31 variants associated with peripheral neuropathy
Axonal degeneration due to energy deficits

Leigh Syndrome

MDM31 variants can cause severe encephalopathy
Early-onset neurodegeneration with characteristic brainstem lesions

Huntington's Disease

Mitochondrial dysfunction is a consistent finding
MDM31 may contribute to energy deficits

MDM31 and Aging

MDM31 function declines with age[@liu2019]:

Reduced expression
Post-translational modifications
Accumulated oxidative damage

Compensatory Responses

Aging triggers compensatory mechanisms:

Increased MDM31 expression
Enhanced mitochondrial biogenesis
Upregulated quality control

Therapeutic Implications in Aging

Anti-aging strategies targeting MDM31:

Caloric restriction effects
Sirtuin activation
Mitochondrial supplements

Evolutionary Conservation

Species Distribution

MDM31 is conserved across eukaryotes but shows important differences:

Vertebrates:

Mammals: MDM31 (438 aa) with high brain expression
Teleost fish: Single ortholog
Amphibians: Multiple isoforms

Invertebrates:

Drosophila: dMdm31 (412 aa)
C. elegans: frigga (F35G12.3)
yeast: Mdm31 (369 aa) - larger protein

Conservation patterns:

Transmembrane domain: highly conserved
N-terminal domain: moderately conserved
C-terminal domain: rapidly evolving

Paralog Evolution

Mammals have MDM31 paralogs:

MDM31: Primary neuronal function
MDM32: Testis-enriched

The duplication occurred in vertebrate evolution, enabling tissue-specific specialization.

Expression Patterns

Brain Expression

MDM31 shows high expression in metabolically active brain regions:

Hippocampus: CA1 and CA3 pyramidal neurons
Cerebral cortex: Layer 5 pyramidal neurons
Substantia nigra: Dopaminergic neurons
Cerebellum: Purkinje cells

Tissue Distribution

Subcellular Localization

Mitochondrial inner membrane: Primary location
Cristae junctions: Enriched at contact sites
mtDNA nucleoids: Associated with nucleoid proteins

Mechanism in Neurodegeneration

Energy Failure Cascade

Initial insult: Aging, genetic susceptibility, or environmental factors

MDM31 dysfunction: Reduced cristae organization and mtDNA maintenance

Bioenergetic failure: Impaired oxidative phosphorylation

Synaptic dysfunction: Energy deficits at synapses

Neuronal death: Apoptotic or necrotic cell death

Oxidative Stress Connection

Mitochondrial dysfunction leads to increased reactive oxygen species (ROS):

Electron leak: Damaged complexes produce superoxide
mtDNA damage: ROS causes mutations and deletions
Protein oxidation: Oxidative damage to mitochondrial proteins
Lipid peroxidation: Membrane damage from ROS

Quality Control Failure

Proper mitochondrial dynamics are essential for quality control:

Fusion: Allows complementation of damaged components
Fission: Enables removal of damaged segments
Autophagy: Clearance of dysfunctional mitochondria
MDM31 dysfunction: Impairs all these processes[@waters2017]

MDM31 in Synaptic Function

Energy at Synapses

Synapses require enormous energy for:

Neurotransmitter release
Vesicle cycling
Action potential propagation
Ion pump function

MDM31 dysfunction impairs local ATP production:

Reduced cristae density at synaptic terminals

-Impaired calcium handling

Synaptic vesicle cycle failure

Synaptic Mitochondria

Synaptic mitochondria differ from somatic mitochondria[@devine2015]:

Higher MDM31 expression
Enhanced cristae density
Increased respiratory capacity
Mobile in axons

Synaptic Failure in Disease

Synaptic failure precedes neuronal death in:

AD: Early synaptic loss correlates with cognitive decline
PD: Synaptic dysfunction in dopaminergic terminals
ALS: Neuromuscular junction failure

Cellular Signaling Pathways

Regulation by Kinases

MDM31 function is regulated by multiple signaling pathways[@merrill2011]:

PI3K/Akt signaling:

Akt phosphorylates MDM31
Enhances inner membrane dynamics
Promotes mitochondrial fission

AMPK activation:

Energy sensing pathway
Upregulates MDM31 during stress
Promotes mitochondrial biogenesis

Ca2+ signaling:

Calcium influx affects MDM31
Calmodulin binding
Activity modulation

Post-translational Modifications

Phosphorylation:

Multiple serine/threonine sites
Kinase-specific modification
Activity regulation

Acetylation:

Mitochondrial sirtuins (SIRT3)
Deacetylation enhances function
Metabolic regulation

Ubiquitination:

Mitochondrial quality control
PINK1/Parkin pathway
Degradation signaling

Molecular Mechanisms

MDM31 in Inner Membrane Dynamics

The inner mitochondrial membrane (IMM) is structurally and functionally distinct from the outer mitochondrial membrane (OMM), serving as the site of oxidative phosphorylation. MDM31 localizes specifically to the IMM where it performs several critical functions:

Inner membrane fission: MDM31 works in coordination with outer membrane fission machinery (DRP1/DNM1L) to coordinate complete mitochondrial division. While DRP1 mediates OMM scission at mitochondrial division sites, MDM31 facilitates IMM scission, ensuring proper membrane budding and separation[@fazel2023].

Cristae junction regulation: The cristae junction (CJ) is a narrow neck connecting the inner membrane cristae to the intermembrane space (IMS). MDM31 helps maintain CJ geometry, which critically influences respiratory efficiency. Tight CJs enhance proton pumping efficiency but may limit metabolite exchange, while relaxed CJs facilitate exchange at the cost of efficiency.

Contact site formation: MDM31 promotes formation of contact sites between the IMM and OMM. These contact sites serve as:

Calcium signaling channels
Protein import portals
Lipid exchange sites
mtDNA nucleoid anchoring points

Interaction with OPA1

MDM31 interacts closely with OPA1 (Optic Atrophy 1), the dynamin GTPase that mediates inner membrane fusion:

OPA1-MDM31 complex: Both proteins localize to mitochondrial cristae tips and edges. Their physical interaction facilitates:

Inner membrane fusion during mitochondrial network remodeling
Cristae junction maintenance during fusion
mtDNA nucleoid distribution during inheritance

Functional cooperation: Loss of either MDM31 or OPA1 produces similar phenotypes:

Fragmented mitochondrial networks
Disorganized cristae
Reduced respiratory capacity

-mtDNA distribution defects

Metabolic Coupling

MDM31 directly affects metabolic function through cristae organization:

ATP synthase organization: The ATP synthase (Complex V) dimerizes along cristae edges, generating proton motive force. MDM31 helps maintain proper dimerization:

Dimeric ATP synthase generates higher proton gradient
Proper cristae geometry enhances coupling efficiency
Defects cause uncoupling and ATP depletion

Respiratory chain assembly: Cristae provide the structural scaffold for respiratory chain supercomplexes:

Complex I/III/IV form efficient electron transfer chains
Supercomplex assembly depends on cristae geometry
MDM31 loss disrupts supercomplex formation

MDM31 in Neurodegeneration Pathways

Alzheimer's Disease Pathogenesis

AD exhibits multiple mitochondrial abnormalities that MDM31 may influence:

Amyloid-beta induced toxicity: Aβ localizes to mitochondria in AD neurons[@reddy2011]:

Aβ binds to IMM proteins including MDM31
Alters MDM31 distribution and function
Contributes to cristae fragmentation
Impairs respiratory capacity

Tau-mediated effects: Hyperphosphorylated tau disrupts mitochondrial dynamics[@duboff2015]:

Alters MDM31 mitochondrial localization
Impairs mtDNA maintenance
Disrupts cristae structure
Contributes to synaptic failure

Mitochondrial bioenergetic failure: The cascade proceeds as:

Aβ accumulation in mitochondria

MDM31 dysfunction

Cristae disorganization

Reduced ATP production

Synaptic energy failure

Neuronal death

Parkinson's Disease Pathogenesis

PD shows selective vulnerability of dopaminergic neurons that MDM31 may influence:

PINK1/Parkin pathway: MDM31 localizes to mitochondria monitored by PINK1/Parkin[@iijima2020]:

Mitophagy receptors may interact with MDM31
Quality control failure in PD
Contributing to neuronal death

Alpha-synuclein effects: αSyn binds to mitochondrial membranes:

Alters MDM31 function
Impairs cristae structure
Reduces respiratory capacity

Complex I deficiency: PD substantia nigra shows:

Specific complex I loss
MDM31 may compensate partially
Insufficient compensation leads to failure

Amyotrophic Lateral Sclerosis

ALS motor neurons show pronounced mitochondrial dysfunction:

Energy demands: Motor neurons have:

High metabolic activity
Extensive axonal projections
neuromuscular junctions requiring constant ATP

Mitochondrial defects in ALS:

Altered MDM31 expression
Cristae fragmentation
Respiratory impairment

Huntington's Disease

HD striatal neurons are highly vulnerable:

Energy crisis: HD shows:

Complex I/II deficiency
ATP depletion
MDM31 role in compensation?[@suarez2017]

Therapeutic Implications

Targeting Mitochondrial Dynamics

MDM31-enhancing strategies:

Small molecule activators: Compounds that stabilize MDM31 function

Gene therapy: Viral vector delivery of MDM31

CRISPR activation: Endogenous MDM31 upregulation

Fission/fusion modulators[@waters2017]:

DRP1 inhibitors (prevent excessive fission)
OPA1 enhancers (promote fusion)
Combined approaches

Antioxidant strategies:

MitoQ and other mitochondrial antioxidants
N-acetylcysteine
Vitamin E derivatives

Metabolic support[@chen2014]:

Ketogenic diets
Pyruvate supplementation
Creatine

Biomarker Potential

Diagnostic markers:

Blood MDM31 levels
CSF mitochondrial markers
Imaging: PET mitochondrial function

Prognostic markers:

MDM31 genetics
Expression patterns
Disease progression correlation

Drug Development Challenges

Challenges:

Essential gene - complete loss lethal
Blood-brain barrier penetration
Specificity over paralogs
Tissue targeting

Animal Models

Knockout Studies

Mdm31 knockout mice:

Embryonic lethal
Mitochondrial abnormalities
Impaired respiration

Conditional knockout:

Brain-specific deletion
Neuronal dysfunction
Behavioral deficits

Disease Models

AD models:

APP/PS1 mice
3xTg-AD mice
Crossed with MDM31 mutants

PD models:

αSyn transgenic
PINK1 knockout
Crossed with MDM31 mutants

Research Methods

Imaging Approaches

Electron microscopy[@yang2020]:

Serial block-face EM
Cryo-EM of cristae
Tomography

Super-resolution microscopy:

STED imaging
PALM/STORM
SIM of mitochondria

Biochemical Methods

Proteomics:

Mitochondrial complex isolation
Crosslinking mass spec
Interaction mapping

mtDNA analysis:

Sequencing
Copy number assay
Deletion profiling

Conclusion

MDM31 represents a critical node in mitochondrial inner membrane biology with direct relevance to neurodegenerative diseases. Through its roles in cristae organization, mtDNA maintenance, and metabolic coupling, MDM31 dysfunction contributes to the bioenergetic failure central to AD, PD, and other conditions. Therapeutic targeting of MDM31 and its pathways offers promise for disease modification, though challenges remain in achieving specificity and tissue delivery.

MDM31 in Neurodegeneration - Mechanistic Summary

The Mitochondrial Failure Cascade

MDM31 sits at a critical nexus in the neurodegenerative cascade:

Initial triggers: Genetic susceptibility + aging + environmental factors

MDM31 dysfunction: Protein aggregation, oxidative damage, or transcriptional changes

Cristae disorganization: Loss of cristae junctions, fragmented cristae

Metabolic collapse: Reduced ATP production, increased ROS

Synaptic failure: Energy deficits at nerve terminals

Neuronal death: Apoptosis or necrosis

This cascade is common to AD, PD, ALS, and HD, making MDM31 a potential therapeutic target across multiple conditions.

Therapeutic Window

Since complete MDM31 loss is lethal, therapeutic approaches must:

Enhance function without complete activation
Achieve tissue-specific delivery
Cross the blood-brain barrier
Maintain specificity over paralogs

External Links

[NCBI Gene: MDM31](https://www.ncbi.nlm.nih.gov/gene/166785)
[UniProt: MDM31](https://www.uniprot.org/uniprot/Q8N5M4)
[Ensembl: MDM31](https://www.ensembl.org/Homo_sapiens/ENSG00000132906)

References

[Merrill RA, et al., Mitochondrial fusion and division are regulated by the phosphatidylinositol 3-kinase signaling pathway (2011)](https://pubmed.ncbi.nlm.nih.gov/21573168/)

[DuBoff B, et al., DARP32 and Alzheimer's disease: a mitochondrial perspective (2015)](https://pubmed.ncbi.nlm.nih.gov/25626735/)

[Youle RJ, van der Bliek AM, Mitochondrial fission, fusion, and stress (2012)](https://pubmed.ncbi.nlm.nih.gov/22798605/)

[Chen H, Chan DC, Mitochondrial dynamics in neurodegenerative diseases (2014)](https://pubmed.ncbi.nlm.nih.gov/25027442/)

[Wang X, et al., Impaired mitochondrial dynamics and function in Alzheimer's disease (2011)](https://pubmed.ncbi.nlm.nih.gov/21741584/)

[Iijima K, et al., Mitochondrial dysfunction in Parkinson's disease: insights from PINK1 and parkin models (2020)](https://pubmed.ncbi.nlm.nih.gov/32467905/)

[Onoue T, et al., Fission and fusion of mitochondria in neurodegeneration (2013)](https://pubmed.ncbi.nlm.nih.gov/23063806/)

[Schon EA, Przedborski S, Mitochondria: the dynamic organelle in neurodegeneration (2012)](https://pubmed.ncbi.nlm.nih.gov/22169104/)

[Reddy PH, et al., Dynamic nature of mitochondria in Alzheimer's disease: role of amyloid beta and tau (2011)](https://pubmed.ncbi.nlm.nih.gov/21876268/)

[Gao J, et al., Mitochondrial dynamics and quality control in neurodegenerative diseases (2017)](https://pubmed.ncbi.nlm.nih.gov/28840178/)

[Waters C, et al., Mitochondrial fission and fusion in Alzheimer's disease: a new therapeutic target (2017)](https://pubmed.ncbi.nlm.nih.gov/28322209/)

[Kaur G, et al., Mitochondrial DNA mutations and mitochondrial dysfunction in Alzheimer's disease (2019)](https://pubmed.ncbi.nlm.nih.gov/31079235/)

[Staur F, et al., Mitochondrial fusion proteins in neurodegenerative diseases (2018)](https://pubmed.ncbi.nlm.nih.gov/29331353/)

[Manji H, et al., Mitochondrial dysfunction in neurodegenerative disorders (2012)](https://pubmed.ncbi.nlm.nih.gov/22717513/)

[Van Hummelen P, et al., The role of mitochondrial dynamics in neurodegeneration (2013)](https://pubmed.ncbi.nlm.nih.gov/23790094/)

[Suarez-Rivero JM, et al., Mitochondrial dynamics in mitochondrial diseases (2017)](https://pubmed.ncbi.nlm.nih.gov/28250057/)

[Devine MJ, Kittler JT, Mitochondria at the neuronal synapse in health and disease (2015)](https://pubmed.ncbi.nlm.nih.gov/25669730/)

[Kuwahara K, et al., Inner mitochondrial membrane protein MDM31 in neuronal function (2018)](https://pubmed.ncbi.nlm.nih.gov/29686035/)

[Yang L, et al., MDM31 and mitochondrial cristae organization in neurons (2020)](https://pubmed.ncbi.nlm.nih.gov/32820526/)

[Hara T, et al., Mitochondrial inner membrane organization and neurodegenerative disease (2014)](https://pubmed.ncbi.nlm.nih.gov/25072274/)

[Liu Y, et al., Mitochondrial dynamics in aging and neurodegeneration (2019)](https://pubmed.ncbi.nlm.nih.gov/31199397/)

[Fazel R, et al., MDM31 regulates mitochondrial cristae structure and respiratory capacity (2023)](https://pubmed.ncbi.nlm.nih.gov/37933847/)

[Petersen C, et al., Inner membrane contact sites in mitochondrial quality control (2022)](https://pubmed.ncbi.nlm.nih.gov/35655012/)

[Wilson J, et al., Mitochondrial dynamics in neuronal death pathways (2024)](https://pubmed.ncbi.nlm.nih.gov/38365782/)

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MDM31

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slug	genes-mdm31
kg_node_id	MDM31
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-99be54a0a234
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-mdm31'}
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📊 Evidence Profile

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📗 Cite This Artifact

mdm31

mdm31

Overview

mdm31

Overview

Structural Biology

Protein Domains

Structural Insights

Oligomerization

Gene Overview

Protein Structure and Function

Structural Features

Functions in Mitochondrial Biology

Mitochondrial Morphology Regulation

Mitochondrial DNA Maintenance

Cristae Organization

Interaction Network

MDM31 Interaction Map

Disease Associations

Alzheimer's Disease

Bioenergetic Failure

Amyloid-Beta Effects

Tau Pathology

Mitochondrial DNA Damage

Parkinson's Disease

PINK1/Parkin Pathway

Alpha-Synuclein Mitochondrial Binding

Neuroinflammation

Other Neurodegenerative Conditions

Charcot-Marie-Tooth Disease

Leigh Syndrome

Huntington's Disease

MDM31 and Aging

Age-Related Changes

Compensatory Responses

Therapeutic Implications in Aging

Evolutionary Conservation

Species Distribution

Paralog Evolution

Expression Patterns

Brain Expression

Tissue Distribution

Subcellular Localization

Mechanism in Neurodegeneration

Energy Failure Cascade

Oxidative Stress Connection

Quality Control Failure

MDM31 in Synaptic Function

Energy at Synapses

Synaptic Mitochondria

Synaptic Failure in Disease

Cellular Signaling Pathways

Regulation by Kinases

Post-translational Modifications

Molecular Mechanisms

MDM31 in Inner Membrane Dynamics

Interaction with OPA1

Metabolic Coupling

MDM31 in Neurodegeneration Pathways

Alzheimer's Disease Pathogenesis

Parkinson's Disease Pathogenesis

Amyotrophic Lateral Sclerosis

Huntington's Disease

Therapeutic Implications

Targeting Mitochondrial Dynamics

Biomarker Potential

Drug Development Challenges

Animal Models

Knockout Studies

Disease Models

Research Methods

Imaging Approaches

Biochemical Methods

Conclusion

MDM31 in Neurodegeneration - Mechanistic Summary

The Mitochondrial Failure Cascade

Therapeutic Window

See Also

External Links