Cited by 209Mitochondrial Function and PathologyAutophagy in Disease and TherapyCell death mechanisms and regulation

Mutations in Fis1 disrupt orderly disposal of defective mitochondria

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Shen, Qinfang, Yamano, Koji, Head, Brian P., Kawajiri, Sumihiro, Cheung, Jesmine T. M., Wang, Chunxin, Cho, Jeong-Hoon, Hattori, Nobutaka +2 more·2014·Molecular Biology of the Cell

Abstract

Mitochondrial fission is mediated by the dynamin-related protein Drp1 in metazoans. Drp1 is recruited from the cytosol to mitochondria by the mitochondrial outer membrane protein Mff. A second mitochondrial outer membrane protein, named Fis1, was previously proposed as recruitment factor, but Fis1(-/-) cells have mild or no mitochondrial fission defects. Here we show that Fis1 is nevertheless part of the mitochondrial fission complex in metazoan cells. During the fission cycle, Drp1 first binds to Mff on the surface of mitochondria, followed by entry into a complex that includes Fis1 and endoplasmic reticulum (ER) proteins at the ER-mitochondrial interface. Mutations in Fis1 do not normally affect fission, but they can disrupt downstream degradation events when specific mitochondrial toxins are used to induce fission. The disruptions caused by mutations in Fis1 lead to an accumulation of large LC3 aggregates. We conclude that Fis1 can act in sequence with Mff at the ER-mitochondrial interface to couple stress-induced mitochondrial fission with downstream degradation processes.

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  • Mutations in FIS1 disrupt downstream mitochondrial degradation events, indicating the importance of this protein in mitochondrial turnover.

    “although mutations in FIS1 disrupt downstream mitochondrial degradation events indicating the importance of this protein in mitochondrial turnover (Shen et al., 2014).”

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Authors
Shen, Q., Yamano, K., Head, B. P., Kawajiri, S., Cheung, J. T. M., Wang, C., Cho, J.-H., Hattori, N., Youle, R. J., & van der Bliek, A. M.
Affiliations
  • University of California, Los Angeles (US)
  • National Institutes of Health (US)
  • Juntendo University (JP)
  • Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095
Venue
Molecular Biology of the Cell
Published
2014-01
Volume
25
Issue
1
Pages
145-159
ISSN
  • 1059-1524 (ISSN-L)
  • 1939-4586
OpenAlex
W2166496519
Cited by
209
References
61
Citations by year
2026: 7 · 2025: 8 · 2024: 14 · 2023: 13 · 2022: 19 · 2021: 29 · 2020: 17 · 2019: 19 · 2018: 16 · 2017: 19 · 2016: 21 · 2015: 16 · 2014: 11
FWCI
7.13
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • Molecular Biology of the Cell (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • National Institute of General Medical Sciences (T32GM007104, R01GM051866, GM-051866)
  • 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
Fis1, mitochondrial fission, Drp1, Mff, mitochondrial outer membrane proteins, mitophagy, mitochondrial toxins, dynamin-related proteins
MeSH terms
Animals, Endoplasmic Reticulum, HeLa Cells, Humans, Membrane Proteins, Microtubule-Associated Proteins, Muscles, Caenorhabditis elegans, Mutation, Missense, Mitochondrial Proteins, Caenorhabditis elegans Proteins, HCT116 Cells, Proteolysis, Mitochondrial Dynamics

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