Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell

X Luo1, I Budihardjo, H Zou

  • 1Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 75235, USA.

Cell
|September 4, 1998
PubMed

Insights

This study identifies Bid as a key protein that relays apoptotic signals. Caspase-8 cleavage of Bid triggers cytochrome c release from mitochondria, initiating programmed cell death.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cell surface death receptors initiate apoptosis.
  • Caspase-8 is an apical caspase activated by these receptors.
  • Mitochondrial outer membrane permeabilization (MOMP) is a critical step in apoptosis.

Purpose of the Study:

  • To identify the cytosolic protein mediating cytochrome c release.
  • To elucidate the role of Bid in the apoptotic pathway.
  • To understand the mechanism of Bid-induced MOMP.

Main Methods:

  • Protein purification from cell extracts.
  • Peptide mass fingerprinting for protein identification.
  • Immunodepletion assays.
  • Analysis of Bid cleavage and translocation.
  • Functional assays for cytochrome c release.

Main Results:

  • A cytosolic protein inducing cytochrome c release was purified and identified as Bid.
  • Caspase-8 cleaves Bid, and the COOH-terminal fragment translocates to mitochondria.
  • Bid triggers cytochrome c release, a process antagonized by Bcl2.
  • A mutation in Bid's BH3 domain reduced its activity.

Conclusions:

  • Bid acts as a crucial intermediary, relaying apoptotic signals from death receptors to mitochondria.
  • Bid-induced cytochrome c release is a key event in the intrinsic apoptotic pathway.
  • Bid's function is regulated by caspase-8 cleavage and interaction with Bcl2.

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