Cited by 370Mitochondrial Function and PathologyAutophagy in Disease and TherapyCell death mechanisms and regulation

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

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Zhao, Jian, Liu, Tong, Jin, Shaobo, Wang, Xinming, Qu, Mingqi, Uhlén, Per, Tomilin, Nikolay, Shupliakov, Oleg +2 more·2011·The EMBO Journal

Abstract

Mitochondrial morphology is controlled by two opposing processes: fusion and fission. Drp1 (dynamin-related protein 1) and hFis1 are two key players of mitochondrial fission, but how Drp1 is recruited to mitochondria and how Drp1-mediated mitochondrial fission is regulated in mammals is poorly understood. Here, we identify the vertebrate-specific protein MIEF1 (mitochondrial elongation factor 1; independently identified as MiD51), which is anchored to the outer mitochondrial membrane. Elevated MIEF1 levels induce extensive mitochondrial fusion, whereas depletion of MIEF1 causes mitochondrial fragmentation. MIEF1 interacts with and recruits Drp1 to mitochondria in a manner independent of hFis1, Mff (mitochondrial fission factor) and Mfn2 (mitofusin 2), but inhibits Drp1 activity, thus executing a negative effect on mitochondrial fission. MIEF1 also interacts with hFis1 and elevated hFis1 levels partially reverse the MIEF1-induced fusion phenotype. In addition to inhibiting Drp1, MIEF1 also actively promotes fusion, but in a manner distinct from mitofusins. In conclusion, our findings uncover a novel mechanism which controls the mitochondrial fusion-fission machinery in vertebrates. As MIEF1 is vertebrate-specific, these data also reveal important differences between yeast and vertebrates in the regulation of mitochondrial dynamics.

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Crossref · 10.1038/emboj.2011.198

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  • MIEF1/MiD51 and MIEF2/MiD49 recruit DRP1 to mitochondria independent of MFF, but inhibit DRP1 GTPase activity, leading to mitochondrial elongation when overexpressed.

    “MIEF1/MiD51 and the variant MIEF2/MiD49 recruit DRP1 to mitochondria independent of MFF, but in contrast to MFF, inhibit DRP1 GTPase activity leading to mitochondrial elongation when MiD49/51 is overexpressed [92, 95, 96].”

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Authors
Zhao, J., Liu, T., Jin, S., Wang, X., Qu, M., Uhlén, P., Tomilin, N., Shupliakov, O., Lendahl, U., & Nistér, M.
Affiliations
  • Karolinska University Hospital (SE)
  • Karolinska Institutet (SE)
Corresponding author
  • Zhao, Jian
  • Lendahl, Urban
  • Nistér, Monica
Venue
The EMBO Journal
Published
2011-06-24
Volume
30
Issue
14
Pages
2762-2778
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
OpenAlex
W1960363048
Cited by
370
References
54
Citations by year
2026: 8 · 2025: 13 · 2024: 14 · 2023: 22 · 2022: 17 · 2021: 30 · 2020: 25 · 2019: 19 · 2018: 27 · 2017: 27 · 2016: 27 · 2015: 33 · 2014: 38 · 2013: 37 · 2012: 26
FWCI
14.04
Type
journal article
Language
en
Open access
Locations
  • The EMBO Journal (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • University of Rochester
  • Cancerfonden
  • Karolinska Institutet
  • Knut och Alice Wallenbergs Stiftelse
  • Vetenskapsrådet
  • Deutsches Zentrum für Neurodegenerative Erkrankungen
  • Barncancerfonden
  • Cancerföreningen i Stockholm
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
MiD51, Drp1, mitochondrial fusion, mitochondrial fission, mitochondrial dynamics, mitochondrial outer membrane, mitochondrial fragmentation, mitofusins
MeSH terms
Cross-Linking Reagents, Cytoplasm, Fluorescent Antibody Technique, Glioma, HeLa Cells, Humans, Immunoenzyme Techniques, Membrane Fusion, Membrane Proteins, Microtubule-Associated Proteins, Mitochondria, Neuroblastoma, Peptide Elongation Factors, Protein Binding, RNA, Messenger, Subcellular Fractions, Tumor Cells, Cultured, Blotting, Western, Apoptosis, Reverse Transcriptase Polymerase Chain Reaction, GTP Phosphohydrolases, Mitochondrial Proteins, Dynamins, RNA, Small Interfering, Immunoprecipitation, Mitochondrial Membranes

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