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Mitochondrial targeting of tBid/Bax: a role for the TOM complex?

M Ott1, E Norberg, B Zhivotovsky

  • 1Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Cell Death and Differentiation
|June 13, 2009
PubMed

Insights

The Bcl-2 family regulates cell death by controlling the release of pro-apoptotic proteins from mitochondria. This review examines how Bax protein is activated and targeted to mitochondria, a crucial step in apoptosis.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Mitochondrial outer membrane permeabilization is central to apoptosis.
  • Bcl-2 family proteins govern this process, regulating the release of pro-apoptotic factors.
  • Activation and mitochondrial targeting of Bax are key, yet incompletely understood, events.

Purpose of the Study:

  • To review recent findings on Bax activation mechanisms.
  • To discuss the targeting of Bax to the mitochondrial outer membrane.
  • To evaluate methods used for studying Bax mitochondrial import.

Main Methods:

  • Literature review of recent research on Bax.
  • Analysis of proposed Bax receptor models (VDAC, TOM complex, cardiolipin).
  • Discussion of experimental techniques for studying Bax localization.

Main Results:

  • Cleavage of Bid initiates a cascade leading to Bax insertion into the mitochondrial outer membrane.
  • Potential receptors for Bax on the outer mitochondrial membrane include VDAC and the TOM complex.
  • Cardiolipin is also implicated as a functional component in Bax targeting.

Conclusions:

  • Understanding Bax targeting is critical for deciphering apoptosis regulation.
  • Multiple factors, including protein receptors and lipids, likely contribute to Bax mitochondrial localization.
  • Further research is needed to elucidate the precise mechanisms and refine experimental approaches.

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