What role does the mitochondria play in the regulation of apoptosis?
Mitochondria regulate caspase activation and cell death through an event termed mitochondrial outer membrane permeabilization (MOMP); this leads to the release of various mitochondrial intermembrane space proteins that activate caspases, resulting in apoptosis.
How do Valinomycin cause cell death?
Valinomycin induces apoptosis in the murine pre-B cell line BAF3, which cannot be inhibited by interleukin-3 addition or Bcl-2 over-expression. This precedes cytoplasmic acidification, which leads to cysteine-active-site protease activation, DNA fragmentation and cell death.
What is the role of the outer mitochondrial membrane in apoptosis?
Although mitochondria are usually considered as supporters of life, they are also involved in cellular death. Mitochondrial outer membrane permeabilization (MOMP) is a crucial event during apoptosis because it causes the release of proapoptotic factors from the mitochondrial intermembrane space to the cytosol.
What does the mitochondria release in apoptosis?
Mitochondria play key roles in activating apoptosis in mammalian cells. Bcl-2 family members regulate the release of proteins from the space between the mitochondrial inner and outer membrane that, once in the cytosol, activate caspase proteases that dismantle cells and signal efficient phagocytosis of cell corpses.
What happens when mPTP opens?
The opening of mPTP results in osmotic swelling, dissipation of the mitochondrial membrane potential, reduced mitochondrial calcium retention capacity, decreased membrane potential, increased ROS production, and eventually, cell death (Fig. 1).
How does valinomycin affect mitochondrial electron transfer?
Accumulation of potassium inside the mitochondria, mediated by the highly specific ionophore valinomycin, promotes an increase in the volume of matrix (evidenced by swelling) and the interaction points between the two mitochondrial membranes are expected to increase.
How does valinomycin affect cellular respiration?
Valinomycin produces higher steady state potassium phosphate swelling which can be reversed to give active shrinkage if mersalyl is added to block the Pi−/OH− antiporter. Respiration declines concurrently. Uncouplers accelerate the shrinkage and restore the respiration.