Involvement of calcineurin in glutamate-induced mitochondrial dynamics in neurons.
Alterations in the morphology and movement of mitochondria influence neuronal viability. However, the precise mechanisms of such alterations are unclear. In this study, we showed calcineurin was involved in the regulation of mitochondrial dynamics. Glutamate stimulation inhibited mitochondrial movement and decreased mitochondrial length in neurons. FK506 and cyclosporine A, calcineurin inhibitors, attenuated the effects of glutamate on mitochondrial dynamics. It was also found that glutamate treatment dephosphorylated, a proapoptotic protein, Bad and promoted its translocation to mitochondria in neurons via calcineurin. These results provide important new insights into intracellular signaling pathways that regulate mitochondrial dynamics and neuronal cell death.
Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Xiao-Jian
XJ
Han
Yun-Fei
YF
Lu
Shun-Ai
SA
Li
Kazuhito
K
Tomizawa
Kohji
K
Takei
Masayuki
M
Matsushita
Hideki
H
Matsui
D000818:Animals; D019703:Calcineurin / Q000378:metabolism*; D065095:Calcineurin Inhibitors; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008164:Luminescent Proteins / Q000235:genetics; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D051025:bcl-Associated Death Protein / Q000187:drug effects / Q000378:metabolism
C494820:Bad protein, mouse; D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D008164:Luminescent Proteins; D051025:bcl-Associated Death Protein; C413663:fluorescent protein 583; D018698:Glutamic Acid; D019703:Calcineurin