Death upon a kiss: mitochondrial outer membrane composition and organelle communication govern sensitivity to BAK/BAX-dependent apoptosis

Thibaud T Renault; Jerry E Chipuk

doi:10.1016/j.chembiol.2013.10.009

Death upon a kiss: mitochondrial outer membrane composition and organelle communication govern sensitivity to BAK/BAX-dependent apoptosis

Chem Biol. 2014 Jan 16;21(1):114-23. doi: 10.1016/j.chembiol.2013.10.009. Epub 2013 Nov 21.

Authors

Thibaud T Renault¹, Jerry E Chipuk²

Affiliations

¹ Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA; Department of Dermatology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA; The Metabolism Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA.
² Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA; Department of Dermatology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA; The Metabolism Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA; The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA. Electronic address: jerry.chipuk@mssm.edu.

Abstract

For stressed cells to induce the mitochondrial pathway of apoptosis, a cohort of pro-apoptotic BCL-2 proteins must collaborate with the outer mitochondrial membrane to permeabilize it. BAK and BAX are the two pro-apoptotic BCL-2 family members that are required for mitochondrial outer membrane permeabilization. While biochemical and structural insights of BAK/BAX function have expanded in recent years, very little is known about the role of the outer mitochondrial membrane in regulating BAK/BAX activity. In this review, we will highlight the impact of mitochondrial composition (both protein and lipid) and mitochondrial interactions with cellular organelles on BAK/BAX function and cellular commitment to apoptosis. A better understanding of how BAK/BAX and mitochondrial biology are mechanistically linked will likely reveal novel insights into homeostatic and pathological mechanisms associated with apoptosis.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Apoptosis*
Humans
Mitochondrial Membranes / chemistry*
Mitochondrial Membranes / metabolism*
Organelles / chemistry
Organelles / metabolism*
bcl-2 Homologous Antagonist-Killer Protein / chemistry
bcl-2 Homologous Antagonist-Killer Protein / metabolism*
bcl-2-Associated X Protein / chemistry
bcl-2-Associated X Protein / metabolism*

Substances

bcl-2 Homologous Antagonist-Killer Protein
bcl-2-Associated X Protein

Abstract

Publication types

MeSH terms

Substances

Grants and funding