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Mitochondria and cell death: outer membrane permeabilization and beyond

Stephen W G Tait1, Douglas R Green

  • 1Department of Immunology, St Jude Childrens Research Hospital, Memphis, Tennessee 38105, USA.

Nature Reviews. Molecular Cell Biology
|August 5, 2010
PubMed

Insights

Mitochondrial outer membrane permeabilization (MOMP) triggers cell death by releasing proteins, but cells can survive MOMP, potentially causing disease. This process is regulated by BCL-2 family proteins and impacts caspase activation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitochondrial outer membrane permeabilization (MOMP) is a key step in apoptosis, enabling the release of intermembrane space (IMS) proteins like cytochrome c.
  • The integrity of the mitochondrial outer membrane is tightly regulated by the B cell lymphoma 2 (BCL-2) protein family, balancing pro-apoptotic and anti-apoptotic factors.

Purpose of the Study:

  • To elucidate the regulatory mechanisms governing IMS protein release and caspase activity following MOMP.
  • To understand the consequences of cellular survival after MOMP, irrespective of caspase activation.

Main Methods:

  • The study focuses on the roles of BCL-2 family proteins, including BCL-2-associated X protein (BAX) and BCL-2 antagonist or killer (BAK), in inducing MOMP.
  • Analysis of downstream events, including IMS protein release and caspase activation, following MOMP induction.

Main Results:

  • MOMP, induced by BAX or BAK, leads to the release of IMS proteins, which are crucial for caspase activation.
  • Cellular survival following MOMP can occur independently of caspase activity, often due to a progressive decline in mitochondrial function.
  • This survival can have significant pathophysiological implications.

Conclusions:

  • MOMP is a critical but complex event in cell death pathways, with multiple layers of regulation.
  • The BCL-2 family plays a central role in controlling MOMP and subsequent apoptotic signaling.
  • Understanding MOMP and its regulation is vital for comprehending cell death and survival, with potential relevance to various diseases.

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