Bid, a critical mediator for apoptosis induced by the activation of Fas/TNF-R1 death receptors in hepatocytes

J Mol Med (Berl). 2000;78(4):203-11. doi: 10.1007/s001090000099.


The Bcl-2 family proteins consist of both antiapoptosis and pro-apoptosis members that regulate apoptosis typically at the mitochondrial level, mainly by controlling the release of cytochrome c and other mitochondrial apoptotic events. However, death signals mediated by Fas/TNF-R1 receptors can usually activate caspases directly, bypassing the need for mitochondria and escaping the regulation by Bcl-2 family proteins. Bid is a novel pro-apoptosis Bcl-2 family protein that is activated by Caspase 8 in response to Fas/TNF-R1 death receptor activation. Activated Bid is translocated to mitochondria and induces cytochrome c release, which in turn activates the downstream caspases. This Bid-mediated pathway is critical in hepatocyte apoptosis induced by Fas/TNF-R1 engagement, where direct activation of cytosolic caspase cascade seems inefficient. The dependence on Bid, and thus on the mitochondrial cytochrome c release, of hepatocyte apoptosis induced by the death receptors also renders it sensitive to the inhibitory regulation by the anti-apoptosis members of the Bcl-2 family proteins, such as Bcl-2 and Bcl-xL. Moreover, the revealing of this death pathway in hepatocytes is important to the understanding of the pathogenesis of a number of hepatic diseases such as hepatitis or endotoxemia-related hepatic failure.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Antigens, CD / metabolism*
  • Apoptosis*
  • BH3 Interacting Domain Death Agonist Protein
  • Carrier Proteins / physiology*
  • Caspases / metabolism
  • Cytochrome c Group / metabolism
  • Hepatocytes / metabolism*
  • Humans
  • Mitochondria, Liver / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Receptors, Tumor Necrosis Factor, Type I
  • fas Receptor / metabolism*


  • Antigens, CD
  • BH3 Interacting Domain Death Agonist Protein
  • BID protein, human
  • Carrier Proteins
  • Cytochrome c Group
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • fas Receptor
  • Caspases