TY - JOUR
T1 - Calcium in cell injury and death
AU - Dong, Zheng
AU - Saikumar, Pothana
AU - Weinberg, Joel M.
AU - Venkatachalam, Manjeri A.
PY - 2006/4/19
Y1 - 2006/4/19
N2 - Loss of Ca2+ homeostasis, often in the form of cytoplasmic increases, leads to cell injury. Depending upon cell type and the intensity of Ca2+ toxicity, the ensuing pathology can be reversible or irreversible. Although multiple destructive processes are activated by Ca 2+, lethal outcomes are determined largely by Ca2+-induced mitochondrial permeability transition. This form of damage is primarily dependent upon mitochondrial Ca2+ accumulation, which is regulated by the mitochondrial membrane potential. Retention of the mitochondrial membrane potential during Ca2+ increases favors mitochondrial Ca2+ uptake and overload, resulting in mitochondrial permeability transition and cell death. In contrast, dissipation of mitochondrial membrane potential reduces mitochondrial Ca2+ uptake, retards mitochondrial permeability transition, and delays death, even in cells with large Ca2+ increases. The rates of mitochondrial membrane potential dissipation and mitochondrial Ca2+ uptake may determine cellular sensitivity to Ca2+ toxicity under pathological conditions, including ischemic injury.
AB - Loss of Ca2+ homeostasis, often in the form of cytoplasmic increases, leads to cell injury. Depending upon cell type and the intensity of Ca2+ toxicity, the ensuing pathology can be reversible or irreversible. Although multiple destructive processes are activated by Ca 2+, lethal outcomes are determined largely by Ca2+-induced mitochondrial permeability transition. This form of damage is primarily dependent upon mitochondrial Ca2+ accumulation, which is regulated by the mitochondrial membrane potential. Retention of the mitochondrial membrane potential during Ca2+ increases favors mitochondrial Ca2+ uptake and overload, resulting in mitochondrial permeability transition and cell death. In contrast, dissipation of mitochondrial membrane potential reduces mitochondrial Ca2+ uptake, retards mitochondrial permeability transition, and delays death, even in cells with large Ca2+ increases. The rates of mitochondrial membrane potential dissipation and mitochondrial Ca2+ uptake may determine cellular sensitivity to Ca2+ toxicity under pathological conditions, including ischemic injury.
KW - Adenosine triphosphate
KW - Apoptosis
KW - Glycine
KW - Ischemia-reperfusion
KW - Mitochondrial permeability transition
KW - Nonesterified fatty acids
UR - http://www.scopus.com/inward/record.url?scp=33645738336&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645738336&partnerID=8YFLogxK
U2 - 10.1146/annurev.pathol.1.110304.100218
DO - 10.1146/annurev.pathol.1.110304.100218
M3 - Review article
C2 - 18039121
AN - SCOPUS:33645738336
SN - 0066-4286
VL - 1
SP - 405
EP - 434
JO - Annual Review of Pathology
JF - Annual Review of Pathology
ER -