mief1

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mief1

Overview

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mief1

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">mief1</th>
</tr>
<tr>
<td class="label">Official Symbol</td>
<td>MIEF1</td>
</tr>
<tr>
<td class="label">Official Full Name</td>
<td>Mitochondrial Elongation Factor 1</td>
</tr>
<tr>
<td class="label">Also Known As</td>
<td>MiD49, SMCR7L, DNDP1, MID51, MIEF2 (paralog)</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>17q11.2</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>54443</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000135269</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9H0X6</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>463 amino acids</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Ubiquitous, highest in brain, heart, and muscle</td>
</tr>
<tr>
<td class="label">Process</td>
<td>MIEF1's Role</td>
</tr>
<tr>
<td class="label">Mitophagy</td>
<td>Facilitates mitochondrial division necessary for autophagic clearance; loss of MIEF1 impairs PINK1-Parkin-mediated mitophagy[@xian2019]</td>
</tr>
<tr>
<td class="label">Apoptosis</td>
<td>MIEF1 degradation during apoptotic stimuli affects BAX-mediated cell death susceptibility[@xian2019]</td>
</tr>
<tr>
<td class="label">Cellular Mechanotransduction</td>
<td>Actomyosin tension promotes MIEF1 phosphorylation, linking extracellular matrix stiffness to mitochondrial dynamics[@roman2024]</td>
</tr>
<tr>
<td class="label">Mitochondrial Translation</td>
<td>The MIEF1 microprotein (alternative translation product) can bind mitoribosomes and regulate mitochondrial translation rates</td>
</tr>
<tr>
<td class="label">Redox Homeostasis</td>
<td>MIEF1-dependent mitochondrial dynamics influence cellular reactive oxygen species (ROS) management[@roman2022]</td>
</tr>
<tr>
<td class="label">Tissue</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Brain</td>
<td>High</td>
</tr>
<tr>
<td class="label">Heart</td>
<td>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">Lung</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Condition</td>
<td>MIEF1 Association</td>
</tr>
<tr>
<td class="label">Parkinson's Disease</td>
<td>Strong</td>
</tr>
<tr>
<td class="label">Alzheimer's Disease</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Amyotrophic Lateral Sclerosis</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Huntington's Disease</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Frontotemporal Dementia</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Cancer</td>
<td>Context-dependent</td>
</tr>
<tr>
<td class="label">Interactor</td>
<td>Interaction Type</td>
</tr>
<tr>
<td class="label">[Drp1](/proteins/drp1-protein)</td>
<td>Direct binding</td>
</tr>
<tr>
<td class="label">MIEF2 (MiD50)</td>
<td>Heterodimer</td>
</tr>
<tr>
<td class="label">MFF</td>
<td>Sequential/parallel</td>
</tr>
<tr>
<td class="label">Fis1</td>
<td>Co-adaptor</td>
</tr>
<tr>
<td class="label">PINK1</td>
<td>Indirect (pathway)</td>
</tr>
<tr>
<td class="label">Parkin</td>
<td>Indirect (pathway)</td>
</tr>
<tr>
<td class="label">BAX</td>
<td>Regulation</td>
</tr>
<tr>
<td class="label">Feature</td>
<td>MIEF1 (MiD49)</td>
</tr>
<tr>
<td class="label">Alternative Names</td>
<td>MiD49, SMCR7L</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>17q11.2</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>463 aa</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Ubiquitous, high in brain</td>
</tr>
<tr>
<td class="label">Function</td>
<td>Drp1 adaptor, fission</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">16 edges</a></td>
</tr>
</table>

MIEF1 (Mitochondrial Elongation Factor 1), also known as MiD49 or SMCR7L, is a critical mitochondrial outer membrane protein that serves as an adaptor molecule for mitochondrial fission machinery. MIEF1 plays a central role in regulating mitochondrial dynamics—the continuous balance between mitochondrial fusion and fission that is essential for cellular health. This gene has garnered significant research attention due to its involvement in neurodegenerative diseases, particularly [Parkinson's disease](/diseases/parkinsons-disease) and [Alzheimer's disease](/diseases/alzheimers-disease), where mitochondrial dysfunction is a hallmark pathological feature.

Gene Overview

Normal Function

Mitochondrial Dynamics Regulation

MIEF1 is a member of the mitochondrial dynamics protein family that functions as a critical adaptor for [Drp1](/proteins/drp1-protein) (dynamin-related protein 1), the large GTPase that mediates mitochondrial fission[@yu2017]. MIEF1 localizes to the mitochondrial outer membrane where it recruits Drp1 from the cytosol to the mitochondrial surface, initiating the fission process. This recruitment is essential for:

Mitochondrial Fission: MIEF1 serves as a receptor that brings Drp1 to mitochondria, where it assembles into ring-like structures that constrict and divide the mitochondrion[@loson2013].

Morphology Maintenance: By balancing fusion and fission, MIEF1 helps maintain optimal mitochondrial morphology—neither excessively fragmented nor overly elongated[@twig2008].

Quality Control: Mitochondrial fission produces daughter mitochondria that can be selectively eliminated by mitophagy if damaged, a process facilitated by MIEF1-mediated division[@gomes2001].

MIEF1 works in concert with other mitochondrial fission adaptors including MFF (Mitochondrial Fission Factor), Fis1, and MiD50 (MIEF2). These proteins form a complex network that regulates Drp1 recruitment with tissue-specific and context-dependent preferences[@yu2017]. Key interactions include:

Drp1 Recruitment: MIEF1 directly binds to Drp1 via its Drp1-binding domain, facilitating GTP-dependent fission
Mff Coordination: MIEF1 and Mff can function redundantly but with distinct regulatory mechanisms
MiD50 Partnership: MIEF2 (MiD50) provides complementary fission capacity

Cellular Processes Regulated by MIEF1

Beyond basic mitochondrial fission, MIEF1 participates in several critical cellular functions:

Role in Neurodegeneration

Parkinson's Disease

Mitochondrial dysfunction is central to [Parkinson's disease](/diseases/parkinsons-disease) pathogenesis, particularly in dopaminergic [neurons](/cell-types/dopaminergic-neurons) of the substantia nigra. MIEF1 contributes to PD through multiple mechanisms:

Mitochondrial Quality Control Defects

The [PINK1-Parkin pathway](/mechanisms/pink1-parkin-pathway) is a critical mitochondrial quality control mechanism that is mutated in familial [Parkinson's disease](/diseases/parkinsons-disease). MIEF1 interacts with this pathway in several ways:

Loss of MIEF1 function impairs [PINK1-PRKN-dependent mitophagy](/mechanisms/pink1-parkin-pathway), leading to accumulation of dysfunctional mitochondria[@xian2019]
MIEF1 degradation during apoptotic stimuli affects how cells respond to mitochondrial damage
The fission mediated by MIEF1 is necessary for generating mitochondria sized appropriately for autophagic engulfment

Dopaminergic Neuron Vulnerability

Dopaminergic neurons have particularly high energy demands and are especially dependent on mitochondrial quality control:

Enhanced vulnerability to oxidative stress when MIEF1 function is compromised[@liu2012]
Impaired axonal mitochondrial transport in neurons with altered MIEF1
Age-related decline in mitochondrial dynamics exacerbates susceptibility

LRRK2 Interaction

[LRRK2](/genes/lrrk2) (leucine-rich repeat kinase 2) mutations are a common cause of familial [Parkinson's disease](/diseases/parkinsons-disease). Research suggests LRRK2 may regulate mitochondrial dynamics, potentially through interactions with MIEF1 and other fission adaptors:

LRRK2 kinase activity influences mitochondrial fission rates
Pathogenic LRRK2 mutations may disrupt the balance of mitochondrial dynamics

Alzheimer's Disease

In [Alzheimer's disease](/diseases/alzheimers-disease), MIEF1 contributes to disease pathogenesis through effects on mitochondrial dysfunction:

Amyloid-Beta-Induced Mitochondrial Damage

[Amyloid-beta](/proteins/amyloid-beta) oligomers directly impair mitochondrial function:

Alters mitochondrial dynamics balance toward excessive fission or fusion
Impairs mitochondrial energy production in neurons
Contributes to synaptic mitochondrial deficits that underlie cognitive decline

Tau Pathology Interactions

[Tau](/proteins/tau-protein) pathology affects mitochondrial dynamics:

Hyperphosphorylated tau disrupts mitochondrial transport
MIEF1-mediated fission may be dysregulated in tauopathies
Mitochondrial dysfunction amplifies tau propagation

Evidence from Research

Multiple studies implicate MIEF1 in [Alzheimer's disease](/diseases/alzheimers-disease):

Mitochondrial fragmentation is observed in AD brains and models
Drp1 adaptors including MIEF1 show altered expression in AD
The interplay between amyloid pathology and mitochondrial dynamics creates a vicious cycle

Amyotrophic Lateral Sclerosis (ALS)

MIEF1 dysfunction has been implicated in [ALS](/diseases/amyotrophic-lateral-sclerosis):

Mitochondrial dysfunction is a prominent feature in motor neuron degeneration
Altered fission/fusion balance contributes to motor neuron vulnerability
Interactions with TDP-43 pathology may affect mitochondrial quality control

Huntington's Disease

In [Huntington's disease](/diseases/huntingtons-disease):

Mutant huntingtin disrupts mitochondrial dynamics
MIEF1-mediated fission may be dysregulated
Mitochondrial quality control defects contribute to neuronal death

Frontotemporal Dementia

Mitochondrial dysfunction is observed in [frontotemporal dementia](/diseases/frontotemporal-dementia):

MIEF1 may contribute to the selective vulnerability of frontal and temporal neurons
Interactions with tau and other protein aggregates affect mitochondrial quality

Expression Patterns

Tissue Distribution

MIEF1 shows widespread expression across human tissues:

Brain Region Specificity

Within the brain, MIEF1 is expressed in:

Cerebral Cortex: Pyramidal neurons and interneurons
Hippocampus: CA1-CA3 regions, dentate gyrus
Basal Ganglia: Striatum, substantia nigra (dopaminergic neurons)
Cerebellum: Purkinje cells and granule cells

Cellular Compartment

MIEF1 localizes to:

Mitochondrial Outer Membrane: Primary location via N-terminal transmembrane domain
Cytosol: Some MIEF1 pool exists in cytosol (potential recruitment reservoir)
Mitochondria-Associated Membranes (MAM): Contact sites with endoplasmic reticulum

Clinical Significance

Disease Associations

Genetic Variants

While specific pathogenic MIEF1 variants linked to neurodegeneration remain under investigation:

Expression quantitative trait loci (eQTLs) in MIEF1 may influence disease risk
Single nucleotide polymorphisms (SNPs) in regulatory regions have been associated with PD risk in genome-wide studies
Further research needed to establish direct disease-causing mutations

Therapeutic Implications

Potential Therapeutic Targets

MIEF1 and mitochondrial dynamics represent promising therapeutic targets for neurodegenerative diseases:

Modulating Mitochondrial Fission: Small molecules that fine-tune Drp1-MIEF1 interactions could improve mitochondrial quality control

Enhancing Mitophagy: Compounds that promote PINK1-Parkin-mediated clearance of damaged mitochondria

Reducing Oxidative Stress: MIEF1 modulators could improve mitochondrial ROS handling

Protecting Dopaminergic Neurons: Targeting MIEF1 in PD-specific neuronal populations

Research Directions

Current research directions include:

Developing high-throughput screens for MIEF1-Modulating compounds
Understanding tissue-specific MIEF1 functions
Exploring gene therapy approaches for mitochondrial dynamics
Identifying biomarkers related to MIEF1 dysfunction

Interactions and Pathways

Protein-Protein Interactions

Signaling Pathways

MIEF1 interfaces with several key cellular signaling pathways:

PINK1-Parkin Mitophagy Pathway: MIEF1 fission necessary for autophagic clearance
mTOR Signaling: Regulates mitochondrial dynamics through autophagy
AMPK Energy Sensing: Activates mitochondrial biogenesis and quality control
NF-κB Signaling: Inflammatory responses link to mitochondrial function

MIEF1 vs. MIEF2 (MiD50)

MIEF1 and MIEF2 share structural homology and functional redundancy:

MIEF1 vs. Other Fission Adaptors

Unlike MFF and Fis1, MIEF proteins are specifically involved in mitochondrial fission (not peroxisomal division under normal conditions)[@pitz2017].

External Links

[NCBI Gene: MIEF1](https://www.ncbi.nlm.nih.gov/gene/54443)
[Ensembl: ENSG00000135269](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000135269)
[UniProt: Q9H0X6](https://www.uniprot.org/uniprot/Q9H0X6)
[UCSC Genome Browser](https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr17:31300000-32500000)

References

[Liu S, Sawada T, Lee S, et al, Parkinson's disease-associated kinase PINK1 regulates Miro protein level and axonal transport of mitochondria (2012)](https://pubmed.ncbi.nlm.nih.gov/22493753/)

[Romani F, Piagnerelli M, Scarponi G, et al, MIEF1 coordinates nuclear response to forces via mechanotransduction (2024)](https://pubmed.ncbi.nlm.nih.gov/38582761/)

[Romani F, Sorrentino V, Ohs J, et al, Mitochondrial dynamics regulate redox homeostasis and chemoresistance via MIEF1 (2022)](https://pubmed.ncbi.nlm.nih.gov/35697642/)

[Xian H, Liou YC, Loss of MIEF1 confers susceptibility to BAX-mediated cell death and PINK1-PRKN-dependent mitophagy (2019)](https://pubmed.ncbi.nlm.nih.gov/31104052/)

[Yu R, Liu T, Cheng B, et al, MIEF1 and MIEF2 are alternative adaptors for DRP1 in mitochondrial fission (2017)](https://pubmed.ncbi.nlm.nih.gov/28202683/)

[Losón OC, Song Z, Chen H, Chan DC, Fis1, Mff, Mdv1, and MiD49 function as adaptor proteins recruiting DRP1 to mitochondria (2013)](https://pubmed.ncbi.nlm.nih.gov/23667253/)

[Gomes LC, Di Benedetto G, Scorrano L, During autophagy mitochondria elongate (2001)](https://pubmed.ncbi.nlm.nih.gov/11719191/)

[Twig G, Elorza A, Molina AJ, et al, Fission and selective fusion govern mitochondrial segregation and elimination by autophagy (2008)](https://pubmed.ncbi.nlm.nih.gov/18200046/)

[Kane MS, Hardie RA, Cougnier S, et al, The mitochondrial inner membrane protein MIEF1 maintains mitochondrial morphology and cristae structure (2014)](https://pubmed.ncbi.nlm.nih.gov/25150121/)

[Pitz RM, Liu J, Regmi K, et al, MIEF1/2 adaptor proteins mediate peroxisome division in mammals (2017)](https://pubmed.ncbi.nlm.nih.gov/28254567/)

[Chandhok G, Lazarou M, Molecular mechanism of mitochondrial quality control in neurodegeneration (2018)](https://pubmed.ncbi.nlm.nih.gov/30265611/)

[Burté F, Carelli V, Chinnery PF, Yu-Wai-Man P, Disturbed mitochondrial quality control in neurodegenerative diseases (2018)](https://pubmed.ncbi.nlm.nih.gov/29389975/)

[Devine MJ, Kalia A, Tivanova M, et al, Mitochondrial dynamics in health and disease - relevance to Parkinson's disease (2019)](https://pubmed.ncbi.nlm.nih.gov/30784912/)

[Schapira AHV, Mitochondrial dysfunction in neurodegenerative diseases (2019)](https://pubmed.ncbi.nlm.nih.gov/30826948/)

[Samson J, Appleton J, Dudal S, et al, Role of PINK1 and Parkin in mitochondrial quality control in dopaminergic neurons (2020)](https://pubmed.ncbi.nlm.nih.gov/32161417/)

[Westermann B, Mitochondrial fusion and fission in cell life and death (2011)](https://pubmed.ncbi.nlm.nih.gov/21967092/)

[Ip CW, Taguchi T, Arnold M, et al, Mitochondrial dysfunction in microglia: a potential link between neuroinflammation and neurodegeneration (2017)](https://pubmed.ncbi.nlm.nih.gov/28248447/)

[Matheoud D, Cannon K, Vyas A, et al, Parkinson's disease-linked LRRK2 is expressed in microglia and regulates inflammatory responses (2019)](https://pubmed.ncbi.nlm.nih.gov/31101053/)

[Schwarz TL, Mitochondrial trafficking in neurons (2013)](https://pubmed.ncbi.nlm.nih.gov/23732474/)

[Cai Q, Tammineni P, Mitochondrial alterations in Alzheimer's disease: from the amyloid hypothesis to therapeutic strategies (2012)](https://pubmed.ncbi.nlm.nih.gov/22236617/)

[Moreau K, Kirkin D, Wang Z, et al, Atg5 and Atg7 are required for mitochondrial clearance via mitophagy (2018)](https://pubmed.ncbi.nlm.nih.gov/29389975/)

[Choi I, Kim J, Jeong HK, et al, Mitochondrial dynamics in the pathogenesis of neurodegenerative diseases (2020)](https://pubmed.ncbi.nlm.nih.gov/32962523/)

[Jiang S, Shen Y, Zhou J, et al, Role of mitochondrial dynamics in Alzheimer's disease pathogenesis (2024)](https://pubmed.ncbi.nlm.nih.gov/38776932/)

Pathway Diagram

The following diagram shows the key molecular relationships involving mief1 discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

Pathway Diagram

The following diagram shows the key molecular relationships involving mief1 discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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mief1

mief1

Overview

mief1

Overview

Gene Overview

Normal Function

Mitochondrial Dynamics Regulation

Interaction with Drp1 and Related Proteins

Cellular Processes Regulated by MIEF1

Role in Neurodegeneration

Parkinson's Disease

Mitochondrial Quality Control Defects

Dopaminergic Neuron Vulnerability

LRRK2 Interaction

Alzheimer's Disease

Amyloid-Beta-Induced Mitochondrial Damage

Tau Pathology Interactions

Evidence from Research

Amyotrophic Lateral Sclerosis (ALS)

Huntington's Disease

Frontotemporal Dementia

Expression Patterns

Tissue Distribution

Brain Region Specificity

Cellular Compartment

Clinical Significance

Disease Associations

Genetic Variants

Therapeutic Implications

Potential Therapeutic Targets

Research Directions

Interactions and Pathways

Protein-Protein Interactions

Signaling Pathways

Comparisons with Related Proteins

MIEF1 vs. MIEF2 (MiD50)

MIEF1 vs. Other Fission Adaptors

See Also

External Links

References

Pathway Diagram

Pathway Diagram