Spatial and temporal association of Bax with mitochondrial fission sites, Drp1, and Mfn2 during apoptosis

By M. Karbowski, Yang-ja Lee, B. Gaume, Seon‐Yong Jeong, S. Frank, A. Nechushtan, A. Santel, M. Fuller, Carolyn L. Smith, R. Youle. Journal of Cell Biology, 2002

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We find that Bax, a proapoptotic member of the Bcl-2 family, translocates to discrete foci on mitochondria during the initial stages of apoptosis, which subsequently become mitochondrial scission sites. A dominant negative mutant of Drp1, Drp1K38A, inhibits apoptotic scission of mitochondria, but does not inhibit Bax translocation or coalescence into foci. However, Drp1K38A causes the accumulation of mitochondrial fission intermediates that are associated with clusters of Bax. Surprisingly, Drp1 and Mfn2, but not other proteins implicated in the regulation of mitochondrial morphology, colocalize with Bax in these foci. We suggest that Bax participates in apoptotic fragmentation of mitochondria.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/04e3e63f0d9deb1996f30328be685058d929a987

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Citations in the corpus

Mitochondrial fragmentation in neurodegeneration (2008, background): “Expression of the dominant-negative DRP1 mutant, DRP1 K38A , in cell lines decreases mitochondrial fragmentation and blocks cell death in response to staurosporine , gamma radiation and etoposide”
Bax, Bak and beyond — mitochondrial performance in apoptosis (2018, background): “Although the role of mitochondrial fission in apoptosis still remains controversial, it is accepted that Drp1 is not required for Bax and Bak activation and foci formation at the mitochondria [99, 106] but that the absence of Drp1 delays cytochrome c release [57, 103, 104, 107].”
Mitochondrial fusion and fission in cell life and death (2010, background): “Furthermore, the observation that the pro-apoptotic proteins BAX and BCL-2 antagonist/killer (BAK) interact with DRP1 and mitofusins points to an intense crosstalk of the machineries of mitochondrial dynamics and apoptosi”
The BCL-2 protein family: opposing activities that mediate cell death (2008, background): “These sites of BAX coalescence often develop into mitochondrial division site”
Mitochondrial fission in apoptosis (2005, background): “, and seem to be in equilibrium between conformations that circumscribe the OMM evenly and those that concentrate into foci at sites of mitochondrial fission and fusio”
The role of mitochondria in apoptosis. (2008, background): “colocalize with Bax in fission foci in different cell types treated with various inducers of stress-dependent apoptosis (94), sug-”
Apoptosis: controlled demolition at the cellular level (2008, background): “Although it has been proposed that mitochondrial fragmentation is linked with the release of intermembrane space proteins from these organelle”
Mitochondrial dynamics in health and disease: mechanisms and potential targets (2023, background): “Given that apoptotic cells display a high fission/fusion ratio, it is believed that fission is an essential part of the apoptotic process.(117) It appears that Drp1 contributes to this fracturing phenotype because previous studies have confirmed that depletion of Drp1 prevents division of mitochondr”
Dynamics of mitochondrial morphology in healthy cells and during apoptosis (2003, background): “Recombinant expression of GFP-tagged Mfn2 revealed that Mfn2 can concentrate in punctate foci on mitochondria at sites of fusion/fission.(58) Truncation of the Cterminal coiled-coil domain (GFP-Mfn2(1-703)) alters the sub-”
Cytochrome c: functions beyond respiration (2008, background): “DRP1 colocalizes with BAX to mitochondrial fission sites following the induction of apoptosi”
Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis. (2004, background): “Inhibition of Drp1 GTPase activity with a dominant negative protein (Drp1 K38A ) prevents the mitochondrial fragmentation seen during apoptosis and delays the process of cell death (Frank et al., 2001; Karbowski et al., 2002), suggesting that mitochondrial fission is a required step in apoptosis.”
The BCL-2 Family Reunion (2010, background): “The combined deletion of BAK and BAX results in reduced fusion whereas fission appears unaffected, yet BAX may also promote fusion by altering MFN2 distribution, mobility, and/or complex assembly (Karbowski et al., 2006).”