mitochondrial outer membrane permeabilization involved in programmed cell death

Definition

Target type: biologicalprocess

The process by which the mitochondrial outer membrane becomes permeable to the passing of proteins and other molecules from the intermembrane space to the cytosol as part of a programmed cell death process. [GO_REF:0000060, GOC:mtg_apoptosis, GOC:pg, GOC:TermGenie, PMID:20151314]

Mitochondrial outer membrane permeabilization (MOMP) is a critical event in programmed cell death, particularly in apoptosis. It involves the disruption of the outer mitochondrial membrane, releasing pro-apoptotic proteins into the cytosol and ultimately leading to caspase activation and cell death. MOMP is tightly regulated by a complex interplay of pro- and anti-apoptotic factors, ensuring that cell death occurs only when necessary. Key steps in MOMP include: 1) **Bax/Bak Activation:** The pro-apoptotic proteins Bax and Bak are normally inactive but become activated in response to apoptotic stimuli. Activated Bax/Bak oligomerize and insert into the mitochondrial outer membrane, forming pores. 2) **Permeability Transition Pore (PTP) Opening:** The PTP is a multi-protein channel in the inner mitochondrial membrane that can be regulated by factors such as calcium, reactive oxygen species (ROS), and ATP/ADP ratios. PTP opening leads to mitochondrial swelling and can contribute to MOMP. 3) **Release of Apoptotic Proteins:** Once the outer mitochondrial membrane is permeabilized, cytochrome c and other pro-apoptotic proteins, such as Smac/DIABLO and AIF, are released into the cytosol. 4) **Caspase Activation:** Cytochrome c binds to Apaf-1, forming the apoptosome, which activates caspase-9, initiating a cascade of caspase activation that ultimately leads to the dismantling of the cell. 5) **Other Mechanisms:** MOMP can also be triggered by other mechanisms, such as the direct action of BH3-only proteins on the outer mitochondrial membrane or the formation of membrane-spanning pores by proteins like tBid. The intricate regulation of MOMP ensures that programmed cell death is tightly controlled and only occurs when appropriate. Disruptions in this process can contribute to various diseases, including cancer and neurodegenerative disorders.'
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Proteins (1)

Compounds (3)