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Apoptosis regulation at the mitochondrial outer membrane

Laura A Gillies1, Tomomi Kuwana

  • 1La Jolla Institute, La Jolla, California, 92037.

Journal of Cellular Biochemistry
|January 24, 2014
PubMed

Insights

Mitochondria regulate programmed cell death (apoptosis) through mitochondrial outer membrane permeabilization (MOMP). Bcl-2 family proteins control MOMP, with Bax and Bak forming pores, while a novel catalyst aids efficient permeabilization.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Mitochondria are central to apoptosis, releasing factors that trigger cell death.
  • Mitochondrial outer membrane permeabilization (MOMP) is a key step, regulated by Bcl-2 family proteins.
  • Bax and Bak mediate MOMP, while pro-survival proteins inhibit it.

Purpose of the Study:

  • To review current understanding of MOMP molecular mechanisms and regulation.
  • To highlight the role of Bcl-2 family proteins in controlling MOMP.
  • To discuss recent clinical applications derived from MOMP research.

Main Methods:

  • This review synthesizes existing research on MOMP.
  • It examines the function of Bcl-2 family proteins, including Bax and Bak.
  • The role of a novel MOMP-regulating catalyst is discussed.

Main Results:

  • MOMP involves Bax and Bak forming likely lipidic pores in the mitochondrial outer membrane.
  • BH3-only proteins activate Bax/Bak, while other Bcl-2 members inhibit permeabilization.
  • A newly identified catalyst is crucial for efficient Bax/Bak-mediated MOMP.

Conclusions:

  • MOMP regulation is complex, involving Bcl-2 family proteins and a catalyst.
  • Mitochondrial dynamics are coordinated with MOMP for efficient protein release.
  • Understanding MOMP offers potential for new clinical strategies in apoptosis-related diseases.
Keywords:
APOPTOSISBcl-2 FAMILY PROTEINSMITOCHONDRIA

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