Distinct Ca2+ thresholds determine cytochrome c release or permeability transition pore opening in brain mitochondria. |
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| Authors: | L Schild G Keilhoff W Augustin G Reiser F Striggow |
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| Affiliation: | Institute of Clinical Chemistry, Department of Pathological Biochemistry, Institute of Medical Neurobiology, Institute of Neurobiochemistry, Medical Faculty, Otto-von-Guericke-University, Magdeburg, Germany. lorenz.schild@medizin.uni-magdeburg.de |
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| Abstract: | In diseases associated with neuronal degeneration, such as Alzheimer's or cerebral ischemia, the cytosolic Ca2+ concentration ([Ca2+]cyt) is pathologically elevated. It is still unclear, however, under which conditions Ca2+ induces either apoptotic or necrotic neuronal cell death. Studying respiration and morphology of rat brain mitochondria, we found that extramitochondrial [Ca2+] above 1 M causes reversible release of cytochrome c, a key trigger of apoptosis. This event was NO-independent but required Ca2+ influx into the mitochondrial matrix. The mitochondrial permeability transition pore (PTP), widely thought to underlie cytochrome c release, was not involved. In contrast to noncerebral tissue, only relatively high [Ca2+] (is approximately equal to 200 M) opened PTP and ruptured mitochondria. Our findings might reflect a fundamental mechanism to protect postmitotic neuronal tissue against necrotic devastation and inflammation. |
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