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Mitochondrial Outer Membrane Permeabilization

  1. Melissa J Parsons,
  2. Douglas R Green

Published Online: 15 SEP 2009

DOI: 10.1002/9780470015902.a0021576

eLS

eLS

How to Cite

Parsons, M. J. and Green, D. R. 2009. Mitochondrial Outer Membrane Permeabilization. eLS. .

Author Information

  1. St. Jude Children's Research Hospital, Memphis, TN, USA

Publication History

  1. Published Online: 15 SEP 2009

Abstract

Defects in apoptosis have dire consequences and can contribute to the development of autoimmune disorders, neurological diseases and cancer. At the centre of the intrinsic apoptotic signalling pathway lies the mitochondrion, which is not only the bioenergetic centre of the cell, but also the cell's reservoir of pro-death factors such as cytochrome c. These proteins reside in the mitochondrial intermembrane space (IMS), and their release from the IMS induces a signalling cascade that leads to the demise of the cell. The critical event governing the release of pro-apoptotic molecules from the IMS is mitochondrial outer membrane permiabilization (MOMP). Although two models exist to explain the execution of MOMP, both models incorporate the widely accepted idea that MOMP is achieved through the coordinated actions of pro- and antiapoptotic members of the Bcl-2 (B-cell lymphoma) family of proteins. In addition, non-Bcl-2 family proteins, mitochondrial dynamics and mitochondrial bioenergetics are also involved in MOMP.

Key Concepts:

  • Apoptosis is one mechanism of cell death, which is characterized by distinct morphological features and occurs in response to specific physiological cues.

  • Apoptosis is a signalling cascade that leads to the demise of the cell.

  • The intrinsic apoptotic signalling cascade is one of the two main apoptotic pathways.

  • Mitochondrial outer membrane permeabilization (MOMP) is the key step in apoptosis that involves the mitochondria.

  • Bcl-2 family proteins are both pro- and antiapoptotic in nature, and are the main regulators of MOMP.

  • Bak or Bax is necessary for MOMP.

  • MOMP leads to the release of pro-death factors from the intermembrane space (IMS), which engage caspases to carry out the apoptotic signalling cascade.

  • Mitochondrial bioenergetics are disrupted during MOMP.

Keywords:

  • apoptosis;
  • Bak;
  • Bax;
  • Bcl-2;
  • mitochondria