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Death upon a kiss: mitochondrial outer membrane composition and organelle communication govern sensitivity to

Thibaud T Renault1, Jerry E Chipuk2

  • 1Department 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.

Chemistry & Biology
|November 26, 2013
PubMed

Insights

Pro-apoptotic proteins BAK and BAX initiate apoptosis by permeabilizing the outer mitochondrial membrane. This review explores how mitochondrial composition and organelle interactions regulate BAK/BAX activity during apoptosis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Apoptosis, or programmed cell death, is crucial for multicellular organism development and homeostasis.
  • The mitochondrial pathway of apoptosis is initiated by the permeabilization of the outer mitochondrial membrane.
  • Pro-apoptotic BCL-2 proteins, specifically BAK (Bcl-2 homologous antagonist/killer) and BAX (Bcl-2-associated X protein), are essential effectors of this process.

Purpose of the Study:

  • To review the current understanding of how the outer mitochondrial membrane regulates the activity of BAK and BAX.
  • To highlight the influence of mitochondrial protein and lipid composition on BAK/BAX function.
  • To explore the role of inter-organelle interactions in modulating BAK/BAX-mediated apoptosis.

Main Methods:

  • Literature review of biochemical and structural studies on BAK/BAX.
  • Analysis of research on mitochondrial membrane composition and its impact on apoptosis.
  • Examination of studies investigating organelle crosstalk in the context of apoptosis.

Main Results:

  • While BAK/BAX functions are increasingly understood, their regulation by the outer mitochondrial membrane remains poorly defined.
  • Mitochondrial lipid and protein composition significantly impacts BAK/BAX oligomerization and membrane insertion.
  • Interactions between mitochondria and other organelles, such as the endoplasmic reticulum, can influence apoptotic signaling.

Conclusions:

  • The outer mitochondrial membrane is not merely a passive scaffold but an active regulator of BAK/BAX-driven apoptosis.
  • Understanding the interplay between mitochondrial biology and BAK/BAX is key to elucidating mechanisms of cell death.
  • This knowledge may reveal novel therapeutic targets for diseases involving dysregulated apoptosis.

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