title: Physiological and Pharmacological Control of BAK, BAX, and Beyond.
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.
authors: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
authors: Mark P A
authors: MPA
authors: Luna-Vargas
authors: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; The Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. Electronic address: jerry.chipuk@mssm.edu.
authors: Jerry Edward
authors: JE
authors: Chipuk
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000737:chemistry / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein
keywords: BCL-2 family; BH3 mimetics; apoptosis; mitochondria; mitochondrial outer membrane permeabilization