The deadly landscape of pro-apoptotic BCL-2 proteins in the outer mitochondrial membrane

Mark P.A. Luna-Vargas, Jerry E. Chipuk

Research output: Contribution to journalReview articlepeer-review

99 Scopus citations


Apoptosis is a biological process that removes damaged, excess or infected cells through a genetically controlled mechanism. This process plays a crucial role in organismal development, immunity and tissue homeostasis, and alterations in apoptosis contribute to human diseases including cancer and auto-immunity. In the past two decades, significant efforts have focused on understanding the function of the BCL-2 proteins, a complex family of pro-survival and pro-apoptotic α-helical proteins that directly control the mitochondrial pathway of apoptosis. Diverse structural investigations of the BCL-2 family members have broadened our mechanistic understanding of their individual functions. However, an often over-looked aspect of the mitochondrial pathway of apoptosis is how the BCL-2 family specifically interacts with and targets the outer mitochondrial membrane to initiate apoptosis. Structural information on the relationship between the BCL-2 family and the outer mitochondrial membrane is missing; likewise, knowledge of the biophysical mechanisms by which the outer mitochondrial membrane affects and effects apoptosis is lacking. In this mini-review, we provide a current overview of the BCL-2 family members and discuss the latest structural insights into BAK/BAX activation and oligomerization in the context of the outer mitochondrial membrane and mitochondrial biology.

Original languageEnglish
Pages (from-to)2676-2689
Number of pages14
JournalFEBS Journal
StatePublished - 1 Jul 2016


  • BAK
  • BAX
  • BCL-2 family
  • MOMP
  • Structure
  • apoptosis
  • lipids
  • membrane
  • mitochondria
  • mitochondrial landscape


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