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Cited by 1,755Mitochondrial Function and PathologyCell death mechanisms and regulationAutophagy in Disease and Therapy

The Role of Dynamin-Related Protein 1, a Mediator of Mitochondrial Fission, in Apoptosis

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Frank, Stephan, Gaume, Brigitte, Bergmann-Leitner, Elke S., Leitner, Wolfgang W., Robert, Everett G., Catez, Frédéric, Smith, Carolyn L., Youle, Richard J.·2001·Developmental Cell
DOI 10.1016/s1534-5807(01)00055-7
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Abstract

In healthy cells, fusion and fission events participate in regulating mitochondrial morphology. Disintegration of the mitochondrial reticulum into multiple punctiform organelles during apoptosis led us to examine the role of Drp1, a dynamin-related protein that mediates outer mitochondrial membrane fission. Upon induction of apoptosis, Drp1 translocates from the cytosol to mitochondria, where it preferentially localizes to potential sites of organelle division. Inhibition of Drp1 by overexpression of a dominant-negative mutant counteracts the conversion to a punctiform mitochondrial phenotype, prevents the loss of the mitochondrial membrane potential and the release of cytochrome c, and reveals a reproducible swelling of the organelles. Remarkably, inhibition of Drp1 blocks cell death, implicating mitochondrial fission as an important step in apoptosis.

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  • Inhibition of Drp1 prevents the decrease in mitochondrial membrane potential and release of cytochrome c in COS-7 cells.

    “another study demonstrated that inhibition of Drp1 prevents the decrease in mitochondrial membrane potential and release of cytochrome c in COS-7 cells (16).”

    From Mitochondrial Fission Contributes to Mitochondrial Dysfunction and Insulin Resistance in Skeletal Muscle (2012) · cites this paper as [16]

  • Overexpression of the dominant-negative mutant Drp1K38A induces mitochondrial fusion and confers resistance to apoptosis by preventing a loss of Δψm and inhibiting cytochrome c release.

    “The role of mitochondrial dynamics in regulating apoptosis is mainly based on the finding that overexpression of the dominant-negative mutant Drp1K38A induces mitochondrial fusion and confers resistance to apoptosis by preventing a loss of Δψm and inhibiting cytochrome c release (Breckenridge et al., 2003; Brooks et al., 2009; Frank et al., 2001; Karbowski et al., 2002).”

    From New insights into the role of mitochondria in aging: mitochondrial dynamics and more (2010) · cites this paper as Frank et al., 2001

  • Silencing of Drp1 expression is not associated with reduced translocation of the pro-apoptotic protein Bax to mitochondria, suggesting that Drp1 functions downstream of Bax during apoptosis.

    “Moreover, these studies revealed that silencing of Drp1 expression was not associated with reduced translocation of the pro-apoptotic protein Bax to mitochondria, suggesting that Drp1 functions downstream of Bax during apoptosis.”

    From New insights into the role of mitochondria in aging: mitochondrial dynamics and more (2010) · cites this paper as Frank et al., 2001

  • Mitochondria in cells undergoing apoptosis are drastically altered and converted from long reticular tubules to small puncta-like organelles.

    “It was first described less than a decade ago that mitochondria in cells undergoing apoptosis are drastically altered and converted from long reticular tubules to small puncta-like organelles (Frank et al., 2001).”

    From New insights into the role of mitochondria in aging: mitochondrial dynamics and more (2010) · cites this paper as Frank et al., 2001

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Authors
Frank, S., Gaume, B., Bergmann-Leitner, E. S., Leitner, W. W., Robert, E. G., Catez, F., Smith, C. L., & Youle, R. J.
Affiliations
  • National Institutes of Health (US)
  • National Institute of Neurological Disorders and Stroke (US)
Corresponding author
Youle, Richard J.
ORCID
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2001-10
Volume
1
Issue
4
Pages
515-525
ISSN
1534-5807 (ISSN-L)
DOI
10.1016/s1534-5807(01)00055-7
OpenAlex
W2147551208
Cited by
1,755
References
62
Citations by year
2026: 24 · 2025: 45 · 2024: 52 · 2023: 64 · 2022: 75 · 2021: 99 · 2020: 104 · 2019: 78 · 2018: 80 · 2017: 93 · 2016: 93 · 2015: 83 · 2014: 94 · 2013: 86 · 2012: 103
FWCI
12.48
Type
journal article
Language
en
Open access
Licence
Locations
  • Developmental Cell (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
Drp1, mitochondrial fission, apoptosis, mitochondrial morphology, mitochondrial membrane potential, cytochrome c release, mitochondrial swelling, dominant-negative mutant, mitochondrial outer membrane
MeSH terms
Animals, Cytochrome c Group, HeLa Cells, Humans, Intracellular Membranes, Membrane Potentials, Microtubule-Associated Proteins, Mitochondria, Mitochondrial Swelling, Phenotype, Proteins, Proto-Oncogene Proteins, Transfection, Microscopy, Immunoelectron, Apoptosis, Proto-Oncogene Proteins c-bcl-2, COS Cells, GTP Phosphohydrolases, Mitochondrial Proteins, Dynamins, bcl-2-Associated X Protein

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