Physiological and Pharmacological Control of BAK, BAX, and Beyond

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

Research output: Contribution to journalReview articlepeer-review

122 Scopus citations

Abstract

Cellular commitment to the mitochondrial pathway of apoptosis is accomplished when proapoptotic B cell chronic lymphocytic leukemia/lymphoma (BCL)-2 proteins compromise mitochondrial integrity through the process of mitochondrial outer membrane permeabilization (MOMP). For nearly three decades, intensive efforts focused on the identification and interactions of two key proapoptotic BCL-2 proteins: BCL-2 antagonist killer (BAK) and BCL-2-associated X (BAX). Indeed, we now have critical insights into which BCL-2 proteins interact with BAK/BAX to either preserve survival or initiate MOMP. In contrast, while mitochondria are targeted by BAK/BAX, a molecular understanding of how these organelles govern BAK/BAX function remains less clear. Here, we integrate recent mechanistic insights of proapoptotic BCL-2 protein function in the context of mitochondrial environment, and discuss current and potential pharmacological opportunities to control MOMP in disease.

Original languageEnglish
Pages (from-to)906-917
Number of pages12
JournalTrends in Cell Biology
Volume26
Issue number12
DOIs
StatePublished - 1 Dec 2016

Keywords

  • BCL-2 family
  • BH3 mimetics
  • apoptosis
  • mitochondria
  • mitochondrial outer membrane permeabilization

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