Calcium in cell injury and death.
Loss of Ca(2+) homeostasis, often in the form of cytoplasmic increases, leads to cell injury. Depending upon cell type and the intensity of Ca(2+) toxicity, the ensuing pathology can be reversible or irreversible. Although multiple destructive processes are activated by Ca(2+), lethal outcomes are determined largely by Ca(2+)-induced mitochondrial permeability transition. This form of damage is primarily dependent upon mitochondrial Ca(2+) accumulation, which is regulated by the mitochondrial membrane potential. Retention of the mitochondrial membrane potential during Ca(2+) increases favors mitochondrial Ca(2+) uptake and overload, resulting in mitochondrial permeability transition and cell death. In contrast, dissipation of mitochondrial membrane potential reduces mitochondrial Ca(2+) uptake, retards mitochondrial permeability transition, and delays death, even in cells with large Ca(2+) increases. The rates of mitochondrial membrane potential dissipation and mitochondrial Ca(2+) uptake may determine cellular sensitivity to Ca(2+) toxicity under pathological conditions, including ischemic injury.
Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, Georgia 30912, USA. zdong@mcg.edu
Zheng
Z
Dong
Pothana
P
Saikumar
Joel M
JM
Weinberg
Manjeri A
MA
Venkatachalam
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D010539:Permeability
D002118:Calcium