TY - JOUR
T1 - Mitochondria as Targets of Apoptosis Regulation by Nitric Oxide
AU - Vieira, Helena
AU - Kroemer, Guido
PY - 2003/10/1
Y1 - 2003/10/1
N2 - In addition to their vital role as the cell's power stations, mitochondria exert an important function in apoptosis. In response to most if not all apoptosis inducers, mitochondrial membranes are permeabilized, leading to the release of potentially toxic proteins, mostly from the intermembrane space to the rest of the cells. Such pro-apoptotic intermembrane proteins include the caspase-independent death effector AIF, as well as cytochrome c, which can trigger the activation of caspases, once it has reached the cytosol. The mitochondrial permeabilization process can be induced by a variety of different xenobiotics, via a direct effect on mitochondrial membranes. Alternatively, mitochondrial permeabilization can be induced by endogenous second messengers, which are elicited in response to stress. The permeabilization process is controlled by the mitochondrial permeability transition pore complex (PTPC), by proteins of the Bcl-2/Bax family, as well as by lipids and metabolites. Nitric oxide (NO) is one of the second messengers that can trigger apoptosis by inducing mitochondrial membrane permeabilization. This effect may involve a direct effect on the PTPC and/or indirect effects secondary to the NO-mediated inhibition of oxidative phosphorylation. This has far-reaching implications for the pathophysiology of NO.
AB - In addition to their vital role as the cell's power stations, mitochondria exert an important function in apoptosis. In response to most if not all apoptosis inducers, mitochondrial membranes are permeabilized, leading to the release of potentially toxic proteins, mostly from the intermembrane space to the rest of the cells. Such pro-apoptotic intermembrane proteins include the caspase-independent death effector AIF, as well as cytochrome c, which can trigger the activation of caspases, once it has reached the cytosol. The mitochondrial permeabilization process can be induced by a variety of different xenobiotics, via a direct effect on mitochondrial membranes. Alternatively, mitochondrial permeabilization can be induced by endogenous second messengers, which are elicited in response to stress. The permeabilization process is controlled by the mitochondrial permeability transition pore complex (PTPC), by proteins of the Bcl-2/Bax family, as well as by lipids and metabolites. Nitric oxide (NO) is one of the second messengers that can trigger apoptosis by inducing mitochondrial membrane permeabilization. This effect may involve a direct effect on the PTPC and/or indirect effects secondary to the NO-mediated inhibition of oxidative phosphorylation. This has far-reaching implications for the pathophysiology of NO.
KW - Adenine nucleotide translocase
KW - Bcl-2
KW - Permeability transition
KW - Programmed cell death
UR - http://www.scopus.com/inward/record.url?scp=0346991918&partnerID=8YFLogxK
U2 - 10.1080/15216540310001639652
DO - 10.1080/15216540310001639652
M3 - Review article
C2 - 14711007
AN - SCOPUS:0346991918
SN - 1521-6543
VL - 55
SP - 613
EP - 616
JO - IUBMB Life
JF - IUBMB Life
IS - 10-11
ER -