title: The deadly landscape of pro-apoptotic BCL-2 proteins in the outer mitochondrial membrane.
abstract: 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.
authors.affiliation: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Mark P A
authors.identifier: 0000-0002-2776-9552
authors.initials: MP
authors.lastname: Luna-Vargas
authors.affiliation: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|The Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Jerry E
authors.initials: JE
authors.lastname: Chipuk
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051336:Mitochondrial Membranes / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53
keywords: BAK; BAX; BCL-2 family; MOMP; Structure; apoptosis; lipids; membrane; mitochondria; mitochondrial landscape