Bax Is Present as a High Molecular Weight Oligomer/Complex in the Mitochondrial Membrane of Apoptotic Cells*

By B. Antonsson, S. Montessuit, Belén Sánchez, J. Martinou. Journal of Biological Chemistry, 2001

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Bax is a Bcl-2 family protein with proapoptotic activity, which has been shown to trigger cytochrome crelease from mitochondria both in vitro and in vivo. In control HeLa cells, Bax is present in the cytosol and weakly associated with mitochondria as a monomer with an apparent molecular mass of 20,000 Da. After treatment of the HeLa cells with the apoptosis inducer staurosporine or UV irradiation, Bax associated with mitochondria is present as two large molecular weight oligomers/complexes of 96,000 and 260,000 Da, which are integrated into the mitochondrial membrane. Bcl-2 prevents Bax oligomerization and insertion into the mitochondrial membrane. The outer mitochondrial membrane protein voltage-dependent anion channel and the inner mitochondrial membrane protein adenosine nucleotide translocator do not coelute with the large molecular weight Bax oligomers/complexes on gel filtration. Bax oligomerization appears to be required for its proapoptotic activity, and the Bax oligomer/complex might constitute the structural entirety of the cytochromec-conducting channel in the outer mitochondrial membrane.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/56dcec5c07c7eada64ca3f54bc011de10edcf394

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Citations in the corpus

Apoptosis defects and chemotherapy resistance: molecular interaction maps and networks (2004, background): “Paradoxically, NF-kB can also induce the transcription of proapoptotic molecules like FasL (CD95L) (Kasibhatla et al., 1999), Fas (CD95) (Andjelkovic et al., 1999), death receptor 6 (DR6) (Kasof et al., 2001), DR4, DR5 (Antonsson et al., 2001) and IkBa (Bessho et al., 1994).”
Bcl-2 family members: intracellular targeting, membrane-insertion, and changes in subcellular localization (2004, background): “In response to an apoptotic stimulus, Bax has been suggested to undergo a conformational change during which an N-terminal epitope is revealed, the TMD is released and the hydrophobic pocket becomes available for oligomerization [50,55,59,60].”
The Bcl-2 family: roles in cell survival and oncogenesis (2003, background): “…conformational changes, whereupon cytosolic Bax translocates and both proteins undergo homo-oligomerization on the outer mitochondrial membrane (Hsu and Youle, 1998; Griffiths et al., 1999, 2001; Antonsson et al., 2001; Nechushtan et al., 2001) and probably also the ER membrane (Zong et al., 2003).”
Membrane binding by tBid initiates an ordered series of events culminating in membrane permeabilization by Bax. (2008, background): “in Membrane Permeabilization by Bax”
Mechanisms of ischemic brain damage. (2008, neutral): “The anti-apoptotic Bcl-2 proteins, Bcl-2 and Bcl-XL, can form heterodimers with Bax, thereby preventing pore formation (Edwards and Dean, 1977; Miyashita and Reed, 1995; Hengartner, 2000; Kroemer and Reed, 2000; Adams and Cory, 2001; Antonsson et al., 2001).”
Ways of dying: multiple pathways to apoptosis. (2003, background): “Bak is present in that membrane even in healthy cells but also changes conformation and forms larger aggregates (Griffiths et al. 1999; Wei et al. 2000; Antonsson et al. 2001; Nechushtan et al. 2001).”
Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. (2002, neutral): “Xenopus mitochondria revious reports (Antonsson et al., 2001).”
Bcl-2-family proteins and the role of mitochondria in apoptosis. (2003, background): “Bax and Bak become oligomerized in the mitochondrial outer membrane both during apoptosis in cells [28,61,62] and in vitro, when recombinant Bid is added to isolated mitochondria [28,63 ], and this oligomerization may be important for the permeabilization function.”
Hierarchical regulation of mitochondrion-dependent apoptosis by BCL-2 subfamilies (2006, background): “Following death stimuli, BAX inserts into the mitochondrial outer membrane (MOM) as homo-oligomers, while BAK also homo-oligomerizes, resulting in the permeabilization of the MOM with release of intermembrane space (IMS) proteins, including cytochrome c”
Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins. (2005, background): “Nevertheless, on receipt of cytotoxic signals, both Bax and Bak change conformation, and Bax translocates to the organellar membranes, where both Bax and Bak then form homooligomers that can associate, leading to membrane permeabilization (Hsu et al. 1997; Wolter et al. 1997; Antonsson et al. 2001; ”