Mitochondria permeability transition

Keywords Ca2+ channel mitochondria permeability transition pore apoptosis... 

Covalent binding and GSH depletion in mitochondria may create a condition that favors induction of mitochondria permeability transition (MPT), which inhibits mitochondria bioenergetics (Hanawa et al. 2008 Masubuchi et al. 2005). MPT is... 

Several oxPC species, such as PGPC, PONPC, and PAzPC, were shown to induce mitochondria dysfunction and promote apopotic cell death. Endogenonsly produced or internalized via the TMEM30a transporter, truncated oxPC can directly intercalate into the mitochondria manbrane and thus induce mitochondria membrane depolarization, swelling, and mitochondria permeability transition (MPT) pore... 

Mitochondria play a central role in response to apoptotic stimuli. There is increasing evidence that altered mitochondrial function is linked to apoptosis and a decreasing mitochondrial transmembrane potential ( Pm) is associated with mitochondria dysfunction. The MPT (mitochondria permeability transition) is a permeability increase of the mitochondria membrane coupled with depolarization of the membrane and disruption of mitochondrial membrane integrity. We measured A Pm using a fluorescent probe DiOC6(3) which specially accumulated in polarized membranes and was monitored by flow... 

Accumulated evidence from recent research indicates that mitochondria-derived factors, such as cytochrome c, have an important role in the apoptosis of some cells. Previous reports show that cytochrome c and caspase-9 participate in Apafl apoptosome, a complex important for caspase-3 activation. Cytochrome c was released from mitochondria of HL-60 cells during treatment with carnosic acid, carnosol or ursolic acid. Previous evidence showed that mitochondria permeability transition (MPT) coupled with depolarization of the membrane potential induces the release of cytochrome c (31-33). It also has been reported that cytochrome c released from mitochondria can precede dissipation of the voltage gradient (the mitochondrial transmembrane potential vi/ ) across the membrane, suggesting that the escape of cytochrome c from mitochondria occurs prior to permeability transition pore opening (loss of mitochondrial transmembrane potential) (34,35). Here we observed the depolarization of the mitochondrial membrane potential in HL-60 cells by treatment with carnosic acid, carnosol, or ursolic acid for Ih. Cytochrome c was released after 3h treatment of carnosic acid, carnosol, or ursolic acid. 

Mitochondria and cell death Although oxidative phosphorylation is a mitochondrial process, most ATP utilization occurs outside of the mitochondrion. ATP synthesized from oxidative phosphorylation is actively transported from the matrix to the intermembrane space by adenine nucleotide translocase (ANT). Porins form voltage-dependent anion channels (VDAC) through the outer mitochondrial membrane for the diffusion of H2O, ATP metabolites, and other ions. Under certain types of stress, ANT, VDAC, and other proteins form a nonspecific open channel known as the mitochondrial permeability transition pore. This pore is associated with events that lead rapidly to necrotic cell death. 

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