tailieunhanh - Báo cáo khoa học: Calcium-dependent mitochondrial function and dysfunction in neurons

Calcium is an extraordinarily versatile signaling ion, encoding cellular responses to a wide variety of external stimuli. In neurons, mitochondria can accumulate enormous amounts of calcium, with the consequence that mitochondrial calcium uptake, sequestration and release play pivotal roles in orchestrating calcium-dependent responses as diverse as gene transcrip-tion and cell death. | MINIREVIEW Calcium-dependent mitochondrial function and dysfunction in neurons Natalia B. Pivovarova and S. Brian Andrews Laboratory of Neurobiology National institute of NeurologicalDisorders and Stroke National institutes of Health Bethesda MD USA Keywords calcium buffering calcium deregulation cell death electron microscopy electron probe microanalysis energy filtering electron microscopy excitotoxicity hippocampal neurons mitochondria permeability transition Correspondence B. Andrews Laboratory of Neurobiology National institute of NeurologicalDisorders and Stroke 49 3A62 49 Convent Drive National institutes of Health Bethesda MD 20892-4477 USA. Fax 1 301 480 1485 Tel 1 301 435 2796 E-mail sba@ Received 10 February 2010 revised 14 May 2010 accepted 22 June 2010 Calcium is an extraordinarily versatile signaling ion encoding cellular responses to a wide variety of external stimuli. In neurons mitochondria can accumulate enormous amounts of calcium with the consequence that mitochondrial calcium uptake sequestration and release play pivotal roles in orchestrating calcium-dependent responses as diverse as gene transcription and cell death. In this review we consider the basic chemistry of calcium as a sticky cation which leads to extremely high bound free ratios and discuss areas of current interest or controversy. Topics addressed include methodologies for measuring local intracellular calcium mitochondrial calcium buffering and loading capacity mitochondrially directed spatial calcium gradients and the role of calcium overload-dependent mitochondrial dysfunction in glutamate-evoked excitotoxic injury and neurodegeneration. Finally we consider the relationship between delayed calcium de-regulation the mitochondrial permeability transition and the generation of reactive oxygen species and propose a unified view of the source specificity and calcium overload models of N-methyl-D-aspartate NMDA receptor-dependent excitotoxicity. Non-NMDA receptor .