tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c.

By M. Wei, T. Lindsten, Vamsi K. Mootha, S. Weiler, A. Gross, M. Ashiya, Craig B. Thompson, S. Korsmeyer. Genes & Development, 2000

1,312 citations recorded by the source corpus.

TNFR1/Fas engagement results in the cleavage of cytosolic BID to truncated tBID, which translocates to mitochondria. Immunodepletion and gene disruption indicate BID is required for cytochrome c release. Surprisingly, the three-dimensional structure of this BH3 domain-only molecule revealed two hydrophobic alpha-helices suggesting tBID itself might be a pore-forming protein. Instead, we demonstrate that tBID functions as a membrane-targeted death ligand in which an intact BH3 domain is required for cytochrome c release, but not for targeting. Bak-deficient mitochondria and blocking antibodies reveal tBID binds to its mitochondrial partner BAK to release cytochrome c, a process independent of permeability transition. Activated tBID results in an allosteric activation of BAK, inducing its intramembranous oligomerization into a proposed pore for cytochrome c efflux, integrating the pathway from death receptors to cell demise.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/48091ae56edb83efe1f5312274a5c0b38f047b43

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Citations in the corpus

Ways of dying: multiple pathways to apoptosis. (2003, background): “It has been proposed that Bid activates Bax and Bak, as well as inactivates pro-survival relatives (Desagher et al. 1999; Gross et al. 1999; Wei et al. 2000).”
Mitochondrial Cristae Shape Determines Respiratory Chain Supercomplexes Assembly and Respiratory Efficiency (2013, methodology): “…et al., 2002). cBID efficiently released cytochrome c from purified mitochon- dria, whereas a BH3 domain G94E mutant was, as expected, inactive (Wei et al., 2000) and the cBIDKKAA mutant released 25%–30% more cytochrome c than the baseline (Figure 1A), a figure close to the amount of free…”
Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis (2003, background): “When a cell is committed to apoptosis, Bax and Bak undergo conformational change, leading to their oligomerization and insertion in the mitochondria outer membrane (Hsu et al., 1997; Gross et al., 1998; Desagher et al., 1999; Griffiths et al., 1999; Wei et al., 2000; Makin et al., 2001).”
Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. (2006, background): “Our results consistently show that ligation of antiapoptotic family members alone is insufficient to induce MOMP.”
PUMA, a novel proapoptotic gene, is induced by p53. (2001, neutral): “(Perez and White, 2000; Wei et al., 2000) remains to be determined.”
OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion. (2006, neutral): “…Laboratory, Center for Human Genetics, Flanders Interuniversity Institute for Biotechnology (VIB4) and K.U. Leuven, Belgium 4Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA *Contact: luca.scorrano@unipd.it DOI 10.1016/j.cell.2006.06.025”
The BCL-2 Family Reunion (2010, background): “The active form of BID (discussed below) promotes BAK and BAX oligomerization, MOMP, and cytochrome c release (Kuwana et al., 2002; Wei et al., 2000).”
BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak. (2001, background): “Active caspase 8 in turn cleaves p22 Bid into the death-promoting p15 tBid, which is then targeted to the mitochondria and binds to either Bax or Bak and results in their oligomerization (Li et al. 1998; Luo et al. 1998; Wei et al. 2000).”
Bax, Bak and beyond — mitochondrial performance in apoptosis (2018, neutral): “According to the ‘kiss-and-run’ model [25, 26], BH3-only”