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Neuroscience ; 141(2): 727-736, 2006 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-16797853

RESUMO

Mitochondria have many roles critical to the function of neurons including the generation of ATP and regulation of intracellular Ca2+. Mitochondrial movement is highly dynamic in neurons and is thought to direct mitochondria to specific cellular regions of increased need and to transport damaged or old mitochondria to autophagosomes. Morphology also varies between individual mitochondria and is modulated by fusion and fission proteins such as mitofusin-1 and dynamin-related protein-1, respectively. Although mitochondrial movement and morphology are thought to be modulated to best meet cellular demands, few regulatory signals have been identified. In this study, we examined how the different cellular environments of synaptically immature and mature rat cortical neurons affect mitochondrial movement, morphology, distribution and function. In younger cells, mitochondria were more mobile, were shorter, occupied a smaller percentage of neuronal processes, and expressed greater mitofusin-1 and lower dynamin-related protein-1 protein levels compared with older cells. However, the number of mitochondria per mum of neuronal process, mitochondrial membrane potential and the amount of basally sequestered mitochondrial Ca2+ were similar. Our results suggest that while mitochondria in young neurons are functionally similar to mature neurons, their enhanced motility may permit faster energy dispersal for cellular demands, such as synaptogenesis. As cells mature, mitochondria in the processes may then elongate and reduce their motility for long-term support of synaptic structures.


Assuntos
Córtex Cerebral/citologia , Mitocôndrias/fisiologia , Neurônios/fisiologia , Neurônios/ultraestrutura , Animais , Proteínas Reguladoras de Apoptose , Western Blotting/métodos , Cálcio/metabolismo , Proteínas Quinases Dependentes de Cálcio-Calmodulina , Células Cultivadas , Proteínas Quinases Associadas com Morte Celular , Proteína 4 Homóloga a Disks-Large , Embrião de Mamíferos , Fura-2/farmacocinética , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Ácido Glutâmico/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Luminescentes/biossíntese , Potenciais da Membrana/fisiologia , Proteínas de Membrana/metabolismo , Mitocôndrias/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Neurônios/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Ratos , Ratos Sprague-Dawley , Sinapses/fisiologia , Sinaptofisina/metabolismo , Fatores de Tempo , Transfecção/métodos
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