Related Experiment Video
Updated: Jun 10, 2026
07:35
Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
Published on: June 1, 2022
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
Summary
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.
Related Concept Videos
01:45Mitochondrial Membranes
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
01:45Mitochondrial Membranes
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
01:30Overview of Cell Death
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
01:16Cellular Injury IV: Necrosis
Necrosis is a form of irreversible cell death caused by severe injury such as ischemia, toxins, or trauma. Unlike programmed cell death, it is an uncontrolled, pathological process that typically provokes inflammation in surrounding tissues.Pathophysiologic ChangesNecrosis begins when cells sustain critical damage, leading to swelling of organelles, particularly mitochondria, and rapid ATP depletion. As energy levels decline, membrane ion pumps fail, leading to calcium influx and eventually,...
01:16Necrosis
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
01:22Cellular Injury V: Apoptosis and Autophagy
Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...