Mitochondrial dynamics and morphological changes control neuronal survival

Abstract

Real-time imaging has revealed that mitochondria exhibit dynamic movement and morphological changes in living cells. However, the regulatory mechanisms involved in these processes and their physiological significance are unclear. We showed that in cultured hippocampal neurons distinctive mitochondrial dynamics and morphological changes were regulated by channel specific Ca²⁺ signaling and these changes control neuronal survival and death. VDCC -associated Ca²⁺ elevation induced by high potassium stimulation triggered immediate cessation of movement and late onset of ring-like morphological changes. By contrast, NMDA receptor-associated Ca²⁺ signaling induced by glutamate stimulation produced a relatively slow onset of movement ceasing and the elongated mitochondria become round in morphology. Glutamate-induced mitochondrial change was accompanied by cytochrome c release and led to excitatory neuronal death. These changes were blocked by calcineurin inhibitors FK506 and cyclosporin A. On the other hand, the VDCC-associated changes appeared to be resistant to the cell death. CaMKI-dependent mitochondrial division and increase of mitochondrial volume contributed to the protective effect. These results demonstrated that mitochondrial dynamics and morphological changes are regulated by channel specific calcium signals and such changes exert critical impact on neuronal functions. [Jpn J Physiol 54 Suppl:S82 (2004)]