The role of VDAC in cell death: Friend or foe?

Kyle S. McCommis, Christopher P. Baines

Research output: Contribution to journalReview articlepeer-review

111 Scopus citations

Abstract

As the voltage-dependent anion channel (VDAC) forms the interface between mitochondria and the cytosol, its importance in metabolism is well understood. However, research on VDAC's role in cell death is a rapidly growing field, unfortunately with much confusing and contradictory results. The fact that VDAC plays a role in outer mitochondrial membrane permeabilization is undeniable, however, the mechanisms behind this remain very poorly understood. In this review, we will summarize the studies that show evidence of VDAC playing a role in cell death. To begin, we will discuss the evidence for and against VDAC's involvement in mitochondrial permeability transition (MPT) and attempt to clarify that VDAC is not an essential component of the MPT pore (MPTP). Next, we will evaluate the remaining literature on VDAC in cell death which can be divided into three models: proapoptotic agents escaping through VDAC, VDAC homo- or hetero-oligomerization, or VDAC closure resulting in outer mitochondrial membrane permeabilization through an unknown pathway. We will then discuss the growing list of modulators of VDAC activity that have been associated with induction/protection against cell death. This article is part of a Special Issue entitled: VDAC structure, function, and regulation of mitochondrial metabolism.

Original languageEnglish
Pages (from-to)1444-1450
Number of pages7
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1818
Issue number6
DOIs
StatePublished - Jun 2012

Keywords

  • Apoptosis
  • Mitochondrion
  • Necrosis
  • Permeability transition
  • VDAC

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