Role of Bax and Bak in mitochondrial morphogenesis

By M. Karbowski, Kristi L. Norris, Megan M. Cleland, Seon‐Yong Jeong, R. Youle. Nature, 2006

637 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c6196af1a0f66ed5e513645d2f6709c98f28749e

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Citations in the corpus

Mitochondrial dynamics in mammalian health and disease. (2009, background): “However, it remains to be determined whether Mib interacts directly with Mfn2 or through Mfn1 interaction, as Mfns form heterodimers and coimmunoprecipitation of Mib with Mfn2 could be due to the presence of endogenous Mfn1 in this immunoprecipitated complex.”
Metabolic control of cell death (2014, background): “Proapoptotic Bcl-2 proteins also promote mitochondrial fusion (19) in a manner that is regulated by their antiapoptotic counterparts (23, 149).”
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).”
Apoptosis: controlled demolition at the cellular level (2008, background): “Apoptosis-associated mitochondrial fragmentation seems to be caused primarily by the conformational changes that occur in BAX and BAK during their assembly into a mitochondrial pore or channel, leading some to speculate that these proteins also have a role in the normal ongoing process of mitochondr”
Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation (2011, positive): “To verify that starvation-induced mitochondrial fusion is independent of Mfn2, we analyzed cells deficient for Bax and Bak (Bax/BakDKO) (31), which have been implicated in the control of Mfn2-mediated mitochondrial fusion (32, 33).”
Mitochondria and cell death: outer membrane permeabilization and beyond (2010, background): “Indeed, other studies have found that BCL-2 family members regulate mitochondrial morphology in healthy cell”
Mitochondria: In Sickness and in Health (2012, background): “Conversely, BCL-2 proteins play regulatory roles inmitochondrial dynamics in healthy cells, where they stimulate fusion (Cleland et al., 2011; Hoppins et al., 2011b; Karbowski et al., 2006; Rolland et al., 2009).”
Functions and dysfunctions of mitochondrial dynamics (2007, background): “BAX and BAK double-knockout cells have fragmented mitochondria due to reduced mitochondrial fusio”
Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in mice (2009, background): “Because Bax and Bak regulate not only apoptosis but also normal cellular functions through mitochondrial fission and fusion machinerie”
Analysis of mitochondrial function in situ in permeabilized muscle fibers, tissues and cells (2008, neutral): “Recently, mitochondria are being considered an integral part of multiple cellular signaling cascade”