Proc Natl Acad Sci U S A 2014 Oct 1;111(41):14782-7. Epub 2014 Oct 1.
National Institute of Biological Sciences, Beijing 102206, China; Graduate School of Peking Union Medical College, Beijing 100730, China; and Chinese Academy of Medical Sciences, Beijing 100730, China
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J Biol Chem 2011 Mar 9;286(11):9382-92. Epub 2010 Dec 9.
Drug Discovery Department, Moffitt Cancer Center, University of South Florida, Tampa, Florida 33612, USA.
A critical hallmark of cancer cell survival is evasion of apoptosis. This is commonly due to overexpression of anti-apoptotic proteins such as Bcl-2, Bcl-X(L), and Mcl-1, which bind to the BH3 α-helical domain of pro-apoptotic proteins such as Bax, Bak, Bad, and Bim, and inhibit their function. We designed a BH3 α-helical mimetic BH3-M6 that binds to Bcl-X(L) and Mcl-1 and prevents their binding to fluorescently labeled Bak- or Bim-BH3 peptides in vitro. Read More
J Biol Chem 2015 Sep 1;290(36):22005-18. Epub 2015 Jul 1.
Bioquant, University of Heidelberg, 69120 Heidelberg, Germany the Systems Biology of Cell Death Mechanisms, German Cancer Research Center, the Department of Surgery, Heidelberg University Hospital, and
Efficient apoptosis requires Bax/Bak-mediated mitochondrial outer membrane permeabilization (MOMP), which releases death-promoting proteins cytochrome c and Smac to the cytosol, which activate apoptosis and inhibit X-linked inhibitor of apoptosis protein (XIAP) suppression of executioner caspases, respectively. We recently identified that in response to Bcl-2 homology domain 3 (BH3)-only proteins and mitochondrial depolarization, XIAP can permeabilize and enter mitochondria. Consequently, XIAP E3 ligase activity recruits endolysosomes into mitochondria, resulting in Smac degradation. Read More
Mol Cell 2008 Aug 7;31(4):557-69. Epub 2008 Aug 7.
La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
Controversy surrounds the role and mechanism of mitochondrial cristae remodeling in apoptosis. Here we show that the proapoptotic BH3-only proteins Bid and Bim induced full cytochrome c release but only a subtle alteration of crista junctions, which involved the disassembly of Opa1 complexes. Both mitochondrial outer membrane permeabilization (MOMP) and crista junction opening (CJO) were caspase independent and required a functional BH3 domain and Bax/Bak. Read More
Mol Cell 2008 Aug;31(4):570-85
Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland.
Bax and Bak promote apoptosis by perturbing the permeability of the mitochondrial outer membrane and facilitating the release of cytochrome c by a mechanism that is still poorly defined. During apoptosis, Bax and Bak also promote fragmentation of the mitochondrial network, possibly by activating the mitochondrial fission machinery. It has been proposed that Bax/Bak-induced mitochondrial fission may be required for release of cytochrome c from the mitochondrial intermembrane space, although this has been a subject of debate. Read More