2012
DOI: 10.1371/journal.pone.0031510
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Translocation of a Bak C-Terminus Mutant from Cytosol to Mitochondria to Mediate Cytochrome c Release: Implications for Bak and Bax Apoptotic Function

Abstract: BackgroundOne of two proapoptotic Bcl-2 proteins, Bak or Bax, is required to permeabilize the mitochondrial outer membrane during apoptosis. While Bax is mostly cytosolic and translocates to mitochondria following an apoptotic stimulus, Bak is constitutively integrated within the outer membrane. Membrane anchorage occurs via a C-terminal transmembrane domain that has been studied in Bax but not in Bak, therefore what governs their distinct subcellular distribution is uncertain. In addition, whether the distinc… Show more

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Cited by 48 publications
(40 citation statements)
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“…Notably, however, all peripherally attached Bak became carbonate resistant following incubation of mitochondria with truncated Bid (tBid) (Figure 1b, lane 4). Thus, Bak activation enhances α9 membrane insertion, as observed for a semi-cytosolic Bak mutant 33 and for Bax. 48 Bak α9 traverses the MOM but does not line a pore following apoptosis.…”
Section: Resultsmentioning
confidence: 68%
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“…Notably, however, all peripherally attached Bak became carbonate resistant following incubation of mitochondria with truncated Bid (tBid) (Figure 1b, lane 4). Thus, Bak activation enhances α9 membrane insertion, as observed for a semi-cytosolic Bak mutant 33 and for Bax. 48 Bak α9 traverses the MOM but does not line a pore following apoptosis.…”
Section: Resultsmentioning
confidence: 68%
“…The swaps were positioned after P187, as placing the Bax C terminus at this position had successfully maintained Bak localization and apoptotic function. 33 Swaps were generated from Bcl-2 and monoamine oxidase A (MOA), as they normally locate to the MOM, 54,55 with BakBcl2 containing two extra residues (RK) used to enhance mitochondrial targeting. 55 Swaps were also generated from BNIP3 and glycophorin A, as their transmembrane domains (TMDs) contain known dimerization motifs (e.g., GxxxG), and the two proteins localize to the MOM and cell membrane, respectively.…”
Section: Resultsmentioning
confidence: 99%
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“…In healthy cells, Bak and Bax exist in inert conformations in which their hydrophobic a5 helices are surrounded by seven or eight amphipathic helices 3,4 . A carboxy (C)-terminal helix, a9, anchors Bak constitutively in the mitochondrial outer membrane (MOM) 5,6 , whereas in Bax, the a9 helix is initially sequestered in the hydrophobic surface groove, rendering Bax largely cytosolic 4,7 . When cells experience sufficient stress, the BH3-only class of Bcl-2 family proteins cause Bak and Bax to undergo a series of conformation changes-collectively referred to as 'activation'-that culminate in dimerization, leading to pore formation in the MOM [8][9][10] .…”
mentioning
confidence: 99%