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      Apoptosis control by death and decoy receptors

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      Current Opinion in Cell Biology
      Elsevier BV

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          Abstract

          The death receptors Fas and tumor necrosis factor receptor 1 (TNFR1) trigger apoptosis upon engagement by their cognate death ligands. Recently, researchers have discovered several novel homologues of Fas and TNFR1: DR 3, 4, 5, and 6 function as death receptors that signal apoptosis, whereas DcR 1, 2, and 3 act as decoys that compete with specific death receptors for ligand binding. Further, mouse gene knockout studies have enabled researchers to delineate some of the signaling pathways that connect death receptors to the cell's apoptotic machinery.

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          Mitochondria and apoptosis.

          A variety of key events in apoptosis focus on mitochondria, including the release of caspase activators (such as cytochrome c), changes in electron transport, loss of mitochondrial transmembrane potential, altered cellular oxidation-reduction, and participation of pro- and antiapoptotic Bcl-2 family proteins. The different signals that converge on mitochondria to trigger or inhibit these events and their downstream effects delineate several major pathways in physiological cell death.
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            Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis.

            We report here that BID, a BH3 domain-containing proapoptotic Bcl2 family member, is a specific proximal substrate of Casp8 in the Fas apoptotic signaling pathway. While full-length BID is localized in cytosol, truncated BID (tBID) translocates to mitochondria and thus transduces apoptotic signals from cytoplasmic membrane to mitochondria. tBID induces first the clustering of mitochondria around the nuclei and release of cytochrome c independent of caspase activity, and then the loss of mitochondrial membrane potential, cell shrinkage, and nuclear condensation in a caspase-dependent fashion. Coexpression of BclxL inhibits all the apoptotic changes induced by tBID. Our results indicate that BID is a mediator of mitochondrial damage induced by Casp8.
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              Programmed cell death in animal development.

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                Author and article information

                Journal
                Current Opinion in Cell Biology
                Current Opinion in Cell Biology
                Elsevier BV
                09550674
                April 1999
                April 1999
                : 11
                : 2
                : 255-260
                Article
                10.1016/S0955-0674(99)80034-9
                10209153
                0d2b4019-0340-4656-915f-40d492012b08
                © 1999

                https://www.elsevier.com/tdm/userlicense/1.0/

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