Dynamic evolution of the adenine nucleotide translocase interactome during chemotherapy-induced apoptosis

Florence Verrier1, Aurélien Deniaud, Morgane Lebras

  • 1CNRS FRE 2445, Université de Versailles/St Quentin, 45, avenue des Etats-Unis, Versailles 78035, France.

Oncogene
|September 21, 2004
PubMed

Insights

The adenine nucleotide translocator (ANT) interacts with various proteins, forming a dynamic complex that regulates cell death. Glutathione-S-transferase (GST) acts as a repressor, inhibiting pore opening during apoptosis.

Area of Science:

  • Mitochondrial biology
  • Cell death pathways
  • Molecular interactions

Background:

  • The mitochondrial permeability transition pore complex (PTPC) regulates mitochondrial membrane permeabilization during apoptosis, necrosis, and autophagy.
  • Adenine nucleotide translocator (ANT) and voltage-dependent anion channel (VDAC) are key PTPC components and targets of proapoptotic inducers.

Purpose of the Study:

  • To identify interacting partners of ANT in normal tissues and human cancer cell lines.
  • To investigate the dynamic changes in ANT interactions during chemotherapy-induced apoptosis.

Main Methods:

  • Co-immunoprecipitation and proteomic analysis were employed to identify ANT-interacting proteins.
  • Changes in protein interactions were monitored during apoptosis induction.

Main Results:

  • Several ANT-interacting partners were identified, including VDAC, Bax, Bcl-2, respiratory chain subunits, PP2A, PLC beta 4, and IP3 receptor.
  • ANT-VDAC interaction remained constant, while other interactions changed during apoptosis.
  • Glutathione-S-transferase (GST) interacted with ANT in normal and cancer cells but was lost during apoptosis induction.
  • GST's interaction loss suggests its role as an endogenous repressor of PTPC and ANT pore opening.

Conclusions:

  • ANT forms a dynamic polyprotein complex with mitochondrial and other organelle proteins (e.g., endoplasmic reticulum).
  • Modifications within the ANT interactome are crucial for coordinating cellular responses to apoptotic stimuli.
  • GST acts as a repressor of PTPC opening, highlighting its role in regulating cell death.

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