Role of Bax and Bak in mitochondrial morphogenesis
Abstract
Bcl-2 family proteins are potent regulators of programmed cell death. Although their intracellular localization to mitochondria and the endoplasmic reticulum has focused research on these organelles, how they function remains unknown. Two members of the Bcl-2 family, Bax and Bak, change intracellular location early in the promotion of apoptosis to concentrate in focal clusters at sites of mitochondrial division. Here we report that in healthy cells Bax or Bak is required for normal fusion of mitochondria into elongated tubules. Bax seems to induce mitochondrial fusion by activating assembly of the large GTPase Mfn2 and changing its submitochondrial distribution and membrane mobility-properties that correlate with different GTP-bound states of Mfn2. Our results show that Bax and Bak regulate mitochondrial dynamics in healthy cells and indicate that Bcl-2 family members may also regulate apoptosis through organelle morphogenesis machineries.
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Mitochondrial fusion is inhibited following MOMP, primarily due to repression of Mfn2 activity by Bax.
“It has been shown that mitochondrial fusion is inhibited following MOMP (Brooks et al., 2007), primarily due to repression of Mfn2 activity by Bax (Karbowski et al., 2002; Karbowski et al., 2006).”
From New insights into the role of mitochondria in aging: mitochondrial dynamics and more (2010) · cites this paper as Karbowski et al., 2006
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- Authors
- Karbowski, M., Norris, K. L., Cleland, M. M., Jeong, S.-Y., & Youle, R. J.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Karbowski, Mariusz
- Youle, Richard J.
- Venue
- Nature
- Published
- 2006-10
- Volume
- 443
- Issue
- 7112
- Pages
- 658-662
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2061114093
- Cited by
- 625
- References
- 27
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 12 · 2023: 14 · 2022: 16 · 2021: 23 · 2020: 27 · 2019: 20 · 2018: 16 · 2017: 34 · 2016: 36 · 2015: 31 · 2014: 38 · 2013: 41 · 2012: 48
- FWCI
- 21.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- AJOU Open Repository (Ajou University) (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- Bax, Bak, Bcl-2 family proteins, mitochondrial fusion, mitochondrial dynamics, mitochondrial tubulation, mitofusin 2, GTPase, apoptosis, mitochondrial division, membrane mobility
- MeSH terms
- Animals, Biological Transport, Cells, Cultured, Mitochondria, Morphogenesis, Gene Expression, GTP Phosphohydrolases, bcl-2 Homologous Antagonist-Killer Protein, bcl-2-Associated X Protein, Mice
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