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

Thibaud T. Renault, Jerry E. Chipuk

Research output: Contribution to journal › Review article › peer-review

66 Scopus citations

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.

Original language	English
Pages (from-to)	114-123
Number of pages	10
Journal	Chemistry and Biology
Volume	21
Issue number	1
DOIs	https://doi.org/10.1016/j.chembiol.2013.10.009
State	Published - 16 Jan 2014

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title = "Death upon a kiss: Mitochondrial outer membrane composition and organelle communication govern sensitivity to BAK/BAX-dependent apoptosis",

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.",

author = "Renault, {Thibaud T.} and Chipuk, {Jerry E.}",

note = "Funding Information: We would like to thank everyone in the Chipuk Laboratory for their assistance and support. This work was supported by NIH grant CA157740 (to J.E.C.), the JJR Foundation (to J.E.C.), the William A. Spivak Fund (to J.E.C.), and the Fridolin Charitable Trust (to J.E.C.). This work was also supported in part by research grant FY13-238 from the March of Dimes Foundation (to J.E.C.).",

year = "2014",

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doi = "10.1016/j.chembiol.2013.10.009",

language = "English",

volume = "21",

pages = "114--123",

journal = "Cell Chemical Biology",

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T2 - Mitochondrial outer membrane composition and organelle communication govern sensitivity to BAK/BAX-dependent apoptosis

AU - Renault, Thibaud T.

AU - Chipuk, Jerry E.

N1 - Funding Information: We would like to thank everyone in the Chipuk Laboratory for their assistance and support. This work was supported by NIH grant CA157740 (to J.E.C.), the JJR Foundation (to J.E.C.), the William A. Spivak Fund (to J.E.C.), and the Fridolin Charitable Trust (to J.E.C.). This work was also supported in part by research grant FY13-238 from the March of Dimes Foundation (to J.E.C.).

PY - 2014/1/16

Y1 - 2014/1/16

N2 - 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.

AB - 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.

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JO - Cell Chemical Biology

JF - Cell Chemical Biology

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

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