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Adenine nucleotide translocase: a component of the phylogenetically conserved cell death machinery

B Zhivotovsky1, L Galluzzi, O Kepp

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

Cell Death and Differentiation
|August 22, 2009
PubMed

Insights

Mitochondrial outer membrane permeabilization (MOMP) and permeability transition (PT) are distinct cell death pathways. New research shows adenine nucleotide translocase (ANT) interacts with Bcl-2 proteins, linking these pathways.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitochondrial membrane permeabilization (MOMP) and permeability transition (PT) are distinct cell death processes.
  • MOMP is linked to apoptosis and PT to necrosis.
  • MOMP was thought to be independent of the permeability transition pore complex (PTPC).

Purpose of the Study:

  • To investigate the role of adenine nucleotide translocase (ANT) isoforms in cell death.
  • To explore the interaction between Bcl-2 family proteins and PTPC components.
  • To elucidate the crosstalk between MOMP and PT pathways.

Main Methods:

  • Studies in Caenorhabditis elegans.
  • Investigating interactions between CED-9 (Bcl-2 protein) and ANT.
  • Analyzing the role of type 2 transglutaminase (TG2) in ANT1 assembly and function.

Main Results:

  • A specific ANT isoform is crucial for cell death in C. elegans.
  • Physical and functional interaction between CED-9 and ANT confirmed.
  • Type 2 transglutaminase (TG2) is essential for ANT1 assembly and function.
  • TG2 may facilitate Bax association with ANT1.

Conclusions:

  • Bcl-2 family proteins and PTPC components are intricately linked.
  • This crosstalk is conserved across species.
  • ANT plays a key role in integrating MOMP and PT pathways.

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