The phosphorylation of Metaxin 1 controls Bak activation during TNFα induced cell death

Cell Signal. 2017 Jan;30:171-178. doi: 10.1016/j.cellsig.2016.11.008. Epub 2016 Nov 12.


The proapoptotic protein Bak is implicated in the execution phase of apoptosis, a cell death program. Bak is essentially mitochondrial and during early steps of apoptosis undergoes conformational changes that lead to its full membrane integration in mitochondria and the subsequent liberation of pro-apoptotic mitochondrial proteins. Little is known about the partners and mechanisms implicated in the activation of Bak. We have recently shown that Bak is incorporated into a Voltage dependent anionic channel of type 2 (VDAC2)/Metaxin 1(Mtx1)/Metaxin 2 (Mtx2) multi-protein complex in both resting and dying cells. Here, we show that, after the induction of apoptosis, Bak switches from its association with Mtx2 and VDAC2 to a closer association with Mtx1. This change of partners is under the control of a tyrosine phosphorylation of Mtx1 by c-Abl.

Keywords: Apoptosis; Bak; Glioma; Metaxins; Mitochondria; Protein import.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Models, Biological
  • Neoplasm Proteins / metabolism
  • Phosphorylation / drug effects
  • Protein Binding / drug effects
  • Proteins / metabolism*
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology*
  • bcl-2 Homologous Antagonist-Killer Protein / metabolism*
  • bcl-2-Associated X Protein / deficiency
  • bcl-2-Associated X Protein / metabolism


  • MTX1 protein, human
  • Neoplasm Proteins
  • Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein