How does calcium lead to apoptosis?
Release of this stored Ca2+ and subsequent uptake by the mitochondria is a mechanism that can trigger apoptosis. Ca2+ accumulation in the mitochondria leads to mitochondrial membrane permeabilization by stimulating the opening of the mitochondrial permeability transition pore (mPTP, Orrenius et al., 2003).
How do mitochondria cause 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.
How can mitochondrial cytosolic calcium cause cell death?
Mitochondrial Ca2+ uptake in combination with NO production triggers the collapse of mitochondrial membrane potential, culminating in delayed cell death. The existence of a pathway that allows mitochondria to accumulate Ca2+ has been firmly established for about 40 years.
How does ceramide induced apoptosis?
Emerging data suggest that radiation acts directly on the plasma membrane of several cell types, activating acid sphingomyelinase, which generates ceramide by enzymatic hydrolysis of sphingomyelin. Ceramide then acts as a second messenger in initiating an apoptotic response via the mitochondrial system.
Which enzyme activated by increase calcium influx that directly leads to apoptosis?
In one scenario, cytosolic Ca2+ elevation can lead to the activation of many Ca2+-dependent enzymes, including calpain and calcineurin, which in turn drive the apoptosis progression by activating downstream proteins.
What is mitochondrial apoptosis?
Specifically, we focus upon the mitochondrial pathway of apoptosis—the most commonly deregulated form of cell death in cancer. In this process, mitochondrial outer membrane permeabilisation or MOMP represents the defining event that irrevocably commits a cell to die.
Does mitochondria swell during apoptosis?
Mitochondrial swelling is a key morphologic feature of oncotic cell death. In oncotic cell death, the outer membrane ruptures, but in apoptotic cell death there appears to be an increase in mitochondrial permeability without rupture of the outer membrane.
What does mitochondria do with calcium?
Calcium handling by mitochondria is a key feature in cell life. It is involved in energy production for cell activity, in buffering and shaping cytosolic calcium rises and also in determining cell fate by triggering or preventing apoptosis.
What happens when calcium enters the mitochondria?
To uptake calcium ions of mitochondria is of significant functional connotation for cells, because calcium ions in mitochondria are involved in energy production, regulatory signals transfer, and mitochondrial permeability transition pore opening and even programmed cell death of apoptosis, further playing more roles …
How is mitochondrial damage responsible for cell injury?
As mitochondria produce ATP, they simultaneously yield reactive oxygen species (ROS), which are harmful free radicals that circulate throughout the cell, the mitochondria, and the body, causing more damage.
How does calcium cause cellular damage?
This elevated intracellular calcium concentration is responsible for cytoskeletal modifications which alter cell shape, the activation of phospholipases which results in perpetuation of membrane damage and finally, mitochondrial calcification.
What causes the overload of mitochondria that causes apoptosis?
As a consequence of CaEP, a process occurring between ER and mitochondria called calcium induced calcium release (CICR) causes the overload of mitochondria, mitochondria membrane permeabilization and apoptosis factors, such as cytochrome C (Cyt. C) and caspases release, which are the hallmarks of apoptosis.
How does calcium overload cause cell death?
A rapid influx of calcium ions leads to mitochondrial overload by Ca 2+, loss of mitochondrial membrane potential causing cytochrome c release, caspase cascade activation and, as a consequence, cell death.
How does the level of calcium affect mitochondrial function?
Moreover, the level of intracellular calcium is both a positive and a negative effector of mitochondrial function. Physiological concentration of calcium is required for the process of oxidative phosphorylation or ATP synthesis, which provide regular cell function [4].
How much cell suspension is needed for apoptosis?
A volume of 270 µl of cell suspension (in the concentration of 6.1 × 10 6 cells/ml) was added to the cuvettes (4 mm gaps) and refilled with 30 µl of calcium stock solution dissolved in HEPES (final concentration of Ca 2+ 1 mM) or 30 µl of HEPES.
