Details for: MIEF1

Gene ID: 54471

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: MIEF1

Ensembl ID: ENSG00000100335

Description: mitochondrial elongation factor 1

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • neural progenitor cell CL0011020
    CSI 5.15
    rCSI 22.67%
    PRS 88.17
  • stem cell CL0000034
    CSI 5.1
    rCSI 4.91%
    PRS 94.16
  • hematopoietic precursor cell CL0008001
    CSI 4.31
    rCSI 4.43%
    PRS 98.09
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 3.9
    rCSI 2.8%
    PRS 99.14
  • pancreatic A cell CL0000171
    CSI 3.38
    rCSI 3.54%
    PRS 96.48
  • hepatocyte CL0000182
    CSI 3.34
    rCSI 5.98%
    PRS 94.39
  • granulocyte monocyte progenitor cell CL0000557
    CSI 3.03
    rCSI 2.63%
    PRS 97.04
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.81
    rCSI 1.96%
    PRS 97.52
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.49
    rCSI 3.21%
    PRS 89.75
  • myeloid leukocyte CL0000766
    CSI 2.44
    rCSI 2.25%
    PRS 97.05
  • promyelocyte CL0000836
    CSI 2.35
    rCSI 3.39%
    PRS 96.74
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.12
    rCSI 1.92%
    PRS 95.47
  • ependymal cell CL0000065
    CSI 2.11
    rCSI 4.28%
    PRS 83.76
  • club cell CL0000158
    CSI 2.04
    rCSI 2.99%
    PRS 93.7
  • colon epithelial cell CL0011108
    CSI 2.01
    rCSI 2.11%
    PRS 94.59
  • basal cell CL0000646
    CSI 1.85
    rCSI 2.48%
    PRS 94.08

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [MIEF1](/details-gene/54471) (Mitochondrial Elongation Factor 1) encodes a key protein located on the mitochondrial outer membrane that regulates mitochondrial dynamics. Functionally, it is involved in the critical processes of mitochondrial fission and fusion, which are essential for maintaining cellular energy homeostasis, metabolism, and apoptosis. The gene's expression profile reveals its significance in a wide array of metabolically active or proliferative cell types. **Overall**, its high significance is noted in progenitor populations such as [neural progenitor cell](/details-cell/CL0011020) and [stem cell](/details-cell/CL0000034), as well as in various immune and specialized metabolic cells, suggesting a fundamental role in cellular maintenance and function across diverse tissues. Research indicates a complex, and at times contradictory, role for [MIEF1](/details-gene/54471), acting as an adaptor protein that recruits the GTPase Drp1 to the mitochondrial surface, with studies reporting its involvement in promoting both mitochondrial fusion ([Link](https://doi.org/10.1038/emboj.2011.198)) and fission ([Link](https://doi.org/10.1038/embor.2011.54), [Link](https://doi.org/10.1074/jbc.m113.479873)). ## Cellular Roles and Expression Landscape The expression pattern of [MIEF1](/details-gene/54471) highlights its importance in cells with high energy demands or significant proliferative capacity. The **Overall** context shows its highest significance in progenitor and stem cell populations, including [neural progenitor cell](/details-cell/CL0011020) (CSI: 5.15), [stem cell](/details-cell/CL0000034) (CSI: 5.10), and [hematopoietic precursor cell](/details-cell/CL0008001) (CSI: 4.31). This is consistent with the critical role of mitochondrial remodeling during cell differentiation and division. Beyond progenitor cells, [MIEF1](/details-gene/54471) is also a significant gene in various differentiated cell types, indicating its broad functional relevance. It shows high significance in immune cells, such as [CD4-positive, alpha-beta memory T cell](/details-cell/CL0000897) (CSI: 3.90) and [plasmacytoid dendritic cell, human](/details-cell/CL0001058) (CSI: 2.81), where mitochondrial dynamics are crucial for activation and metabolic reprogramming. Furthermore, its notable expression in metabolically specialized cells like [pancreatic A cell](/details-cell/CL0000171) (CSI: 3.38) and [hepatocyte](/details-cell/CL0000182) (CSI: 3.34) underscores its role in managing the mitochondrial network to meet high energetic and biosynthetic demands. The wide-ranging expression across neural, hematopoietic, metabolic, and epithelial lineages suggests [MIEF1](/details-gene/54471) is a fundamental component of mitochondrial quality control and function. ## Pathways and Molecular Function [MIEF1](/details-gene/54471) is principally associated with the regulation of mitochondrial morphology. Gene Ontology annotations place it centrally within the processes of mitochondrial fission ([GO:0000266](https://www.ebi.ac.uk/QuickGO/term/GO:0000266)) and mitochondrial fusion ([GO:0008053](https://www.ebi.ac.uk/QuickGO/term/GO:0008053)). It is localized to the mitochondrial outer membrane ([GO:0005741](https://www.ebi.ac.uk/QuickGO/term/GO:0005741)), where it acts as a receptor or adaptor for other core machinery proteins. The molecular function of [MIEF1](/details-gene/54471) is a subject of ongoing research with some conflicting reports. Several studies identify it as a protein that recruits the dynamin-related protein 1 (Drp1), a master regulator of mitochondrial fission ([Link](https://doi.org/10.1038/embor.2011.54), [Link](https://doi.org/10.1074/jbc.m113.479873)). In this model, [MIEF1](/details-gene/54471), along with other adaptors like Mff and Fis1, facilitates the assembly of Drp1 oligomers on the mitochondrial surface to constrict and divide the organelle. Conversely, another key study reported that human [MIEF1](/details-gene/54471) sequesters Drp1 in a non-productive manner, thereby inhibiting fission and promoting a net state of mitochondrial fusion ([Link](https://doi.org/10.1038/emboj.2011.198)). This dual-reported function suggests that the activity of [MIEF1](/details-gene/54471) may be context-dependent, potentially regulated by post-translational modifications or the relative abundance of other binding partners. Its annotated molecular functions, including ADP binding ([GO:0043531](https://www.ebi.ac.uk/QuickGO/term/GO:0043531)) and GDP binding ([GO:0019003](https://www.ebi.ac.uk/QuickGO/term/GO:0019003)), are consistent with its role in a GTPase-driven mechanochemical process. ## Research Directions The widespread importance of [MIEF1](/details-gene/54471) in regulating mitochondrial dynamics across diverse cell types, coupled with conflicting reports on its precise function, presents several avenues for future research. **Proposed Hypotheses:** 1. Given its high significance in progenitor populations ([neural progenitor cell](/details-cell/CL0011020), [stem cell](/details-cell/CL0000034)), it is hypothesized that [MIEF1](/details-gene/54471) is a critical regulator of the metabolic switch from glycolysis to oxidative phosphorylation during cellular differentiation. Its depletion would likely impair mitochondrial network maturation, trapping progenitor cells in an undifferentiated state or leading to apoptosis. 2. The contradictory roles of [MIEF1](/details-gene/54471) in promoting either fission or fusion may be reconciled by cell-type specific post-translational modifications (PTMs). It is hypothesized that the phosphorylation state of [MIEF1](/details-gene/54471), as suggested by phosphoproteomic studies ([Link](https://doi.org/10.1016/j.molcel.2008.07.007)), dictates its binding affinity for pro-fission (e.g., Drp1) versus pro-fusion (e.g., mitofusins) machinery, thereby acting as a molecular switch to fine-tune mitochondrial dynamics in response to cellular signals. **Experimental Approach:** To test the second hypothesis, one could employ a site-directed mutagenesis approach. Phosphorylation sites on [MIEF1](/details-gene/54471) identified in mass spectrometry datasets would be mutated to create phosphomimetic (e.g., serine to aspartic acid) and phospho-dead (e.g., serine to alanine) variants. These constructs would be expressed in a cell line with clear mitochondrial morphology (e.g., U2OS). The effect of each mutant on the mitochondrial network (fragmented vs. elongated) would be quantified using confocal microscopy and image analysis software. Concurrently, co-immunoprecipitation followed by mass spectrometry would be performed for each mutant to identify its differential protein interactome, specifically assessing its binding to key fission (Drp1, Mff) and fusion (MFN1/2, OPA1) regulators. **Therapeutic Potential:** As a central node in mitochondrial quality control, a process frequently dysregulated in cancer, neurodegeneration, and metabolic diseases, [MIEF1](/details-gene/54471) represents a potential therapeutic target. Its broad expression in healthy tissues, including [hepatocyte](/details-cell/CL0000182) and immune cells, poses a significant challenge for systemic therapy due to the risk of on-target toxicity. However, if certain cancers demonstrate a specific addiction to [MIEF1](/details-gene/54471)-mediated mitochondrial fission for proliferation and metabolic adaptation, developing targeted inhibitors could be a viable strategy. Such a therapeutic would likely involve **inhibition** to disrupt the mitochondrial plasticity required for tumor growth and survival.

Genular Protein ID: 803735847

Symbol: MID51_HUMAN

Name: Mitochondrial dynamics protein of 51 kDa

UniProtKB Accession Codes:

Q9NQG6 Q52MA5 Q7L890 Q9BUI3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 6 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 8 Ensembl 4 EvolutionaryTrace 1 ExpressionAtlas 1 GO 10 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 7 PDBsum 7 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 7 SMART 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12529303

Title: Reevaluating human gene annotation: a second-generation analysis of chromosome 22.

PubMed ID: 12529303

DOI: 10.1101/gr.695703

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 10591208

Title: The DNA sequence of human chromosome 22.

PubMed ID: 10591208

DOI: 10.1038/990031

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 18691976

Title: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.

PubMed ID: 18691976

DOI: 10.1016/j.molcel.2008.07.007

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 21508961

Title: MiD49 and MiD51, new components of the mitochondrial fission machinery.

PubMed ID: 21508961

DOI: 10.1038/embor.2011.54

PubMed ID: 21701560

Title: Human MIEF1 recruits Drp1 to mitochondrial outer membranes and promotes mitochondrial fusion rather than fission.

PubMed ID: 21701560

DOI: 10.1038/emboj.2011.198

PubMed ID: 23921378

Title: MiD49 and MiD51 can act independently of Mff and Fis1 in Drp1 recruitment and are specific for mitochondrial fission.

PubMed ID: 23921378

DOI: 10.1074/jbc.m113.479873

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 23283981

Title: Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission.

PubMed ID: 23283981

DOI: 10.1091/mbc.e12-10-0721

PubMed ID: 23530241

Title: Interchangeable adaptors regulate mitochondrial dynamin assembly for membrane scission.

PubMed ID: 23530241

DOI: 10.1073/pnas.1300855110

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 25621764

Title: Translation of 5' leaders is pervasive in genes resistant to eIF2 repression.

PubMed ID: 25621764

DOI: 10.7554/elife.03971

PubMed ID: 29083303

Title: Deep transcriptome annotation enables the discovery and functional characterization of cryptic small proteins.

PubMed ID: 29083303

DOI: 10.7554/elife.27860

PubMed ID: 31666358

Title: The mitochondrial acyl-carrier protein interaction network highlights important roles for LYRM family members in complex I and mitoribosome assembly.

PubMed ID: 31666358

DOI: 10.1074/mcp.ra119.001784

PubMed ID: 24515348

Title: Structural and functional analysis of MiD51, a dynamin receptor required for mitochondrial fission.

PubMed ID: 24515348

DOI: 10.1083/jcb.201311014

PubMed ID: 33632269

Title: Dominant mutations in MIEF1 affect mitochondrial dynamics and cause a singular late onset optic neuropathy.

PubMed ID: 33632269

DOI: 10.1186/s13024-021-00431-w

Sequence Information:

  • Length: 463
  • Mass: 51293
  • Checksum: 0824AD44305C234D
  • Sequence:
    • MAGAGERKGK KDDNGIGTAI DFVLSNARLV LGVGGAAMLG IATLAVKRMY DRAISAPTSP 
TRLSHSGKRS WEEPNWMGSP RLLNRDMKTG LSRSLQTLPT DSSTFDTDTF CPPRPKPVAR 
KGQVDLKKSR LRMSLQEKLL TYYRNRAAIP AGEQARAKQA AVDICAELRS FLRAKLPDMP 
LRDMYLSGSL YDDLQVVTAD HIQLIVPLVL EQNLWSCIPG EDTIMNVPGF FLVRRENPEY 
FPRGSSYWDR CVVGGYLSPK TVADTFEKVV AGSINWPAIG SLLDYVIRPA PPPEALTLEV 
QYERDKHLFI DFLPSVTLGD TVLVAKPHRL AQYDNLWRLS LRPAETARLR ALDQADSGCR 
SLCLKILKAI CKSTPALGHL TASQLTNVIL HLAQEEADWS PDMLADRFLQ ALRGLISYLE 
AGVLPSALNP KVNLFAELTP EEIDELGYTL YCSLSEPEVL LQT

Genular Protein ID: 39676612

Symbol: B0QY95_HUMAN

Name: N/A

UniProtKB Accession Codes:

B0QY95

Database IDs:

ARBA 3 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 2 GO 2 Gene3D 2 GeneTree 1 HGNC 1 InterPro 3 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 2 Proteomes 2 ProteomicsDB 2 RefSeq 1 SAM 2 SMART 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 10591208

Title: The DNA sequence of human chromosome 22.

PubMed ID: 10591208

DOI: 10.1038/990031

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 11181995

Title: The sequence of the human genome.

PubMed ID: 11181995

DOI: 10.1126/science.1058040

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 18477386

Title: Finishing the finished human chromosome 22 sequence.

PubMed ID: 18477386

DOI: 10.1186/gb-2008-9-5-r78

PubMed ID: 18691976

Title: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.

PubMed ID: 18691976

DOI: 10.1016/j.molcel.2008.07.007

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

Sequence Information:

  • Length: 478
  • Mass: 53332
  • Checksum: 4F880DF6E252DE48
  • Sequence:
    • MAGAGERKGK KDDNGIGTAI DFVLSNARLV LGVGGAAMLG IATLAVKRMY DRAISAPTSP 
TRLSHSGKRS WEEPNWMGSP RLLNRDMKTG LSRSLQTLPT DSSTFDTDTF CPPRPKPVAR 
KGQVDLKKSR LRMSLQEKLL TYYRNRAAIP AGEQARAKQA AVDICAELRS FLRAKLPDMP 
LRDMYLSGSL YDDLQVVTAD HIQLIVPLVL EQNLWSCIPG EDTIMNVPGF FLVRRENPEY 
FPRGSSYWDR CVVGGYLSPK TVADTFEKVV AGSINWPAIG SLLDYVIRPA PPPEALTLEV 
QYERDKHLFI DFLPSVTLGD TVLVAKPHRL AQYDNLWRLS LRPAETARLR ALDQADSGCR 
SLCLKILKAI CKSTPALGHL TASQLTNVIL HLAQEEADWS PDMLADRFLQ ALRGLISYLE 
AGVLPSALNP KDKALKERSL RHQVRMMEVD SRLNVSWKIQ SLVGVWWPCF LPRQALLF

Genular Protein ID: 2261053548

Symbol: Q9H0J7_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q9H0J7

Database IDs:

ARBA 3 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 3 Gene3D 2 InterPro 3 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 2 RefSeq 1 SAM 2 SMART 1

Sequence Information:

  • Length: 478
  • Mass: 53357
  • Checksum: A1624D52F308C892
  • Sequence:
    • MAGAGERKGK KDDNGIGTAI DFVLSNARLV LGVGGAAMLG IATLAVKRMY DRAISAPTSP 
TRLSHSGKRS WEEPNWMGSP RLLNRDMKTG LSRSLQTLPT DSSTFDTDTF CPPRPKPVAR 
KGQVDLKKSR LRMSLQEKLL TYYRNRAAIP AGEQARAKQA AVDICAELRS FLRAKLPDMP 
LRDMYLSGSL YDDLQVVTAD HIQLIVPLVL EQNLWSCIPG EDTIMNVPGF FLVRRENPEY 
FPRGSSYWDR CVVGGYLSPK TVANTFEKVV AGSINWPAIG SLLDYVIRPA PPPEALTLEV 
QYERDKHLFI DFLPSVTLGD TVLVAKPHRL AQYDNLWRLS LRPAETARLR ALDQADSGCR 
SLCLKILKAI CKSTPALGHL TASQLTNVIL HLAQEEADWS PDMLADRFLQ ALRGLISYLE 
AGVLPSALNP KDKALKERSL RYQVRMMEVD SRLNVSWKIQ SLVGVWWPCF LPRQALLF