Knott Andrew B, Perkins Guy, Schwarzenbacher Robert, Bossy-Wetzel Ella
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, 4000 Central Florida Boulevard, Orlando, Florida 32816, USA.
Nat Rev Neurosci. 2008 Jul;9(7):505-18. doi: 10.1038/nrn2417.
Mitochondria are remarkably dynamic organelles that migrate, divide and fuse. Cycles of mitochondrial fission and fusion ensure metabolite and mitochondrial DNA mixing and dictate organelle shape, number and bioenergetic functionality. There is mounting evidence that mitochondrial dysfunction is an early and causal event in neurodegeneration. Mutations in the mitochondrial fusion GTPases mitofusin 2 and optic atrophy 1, neurotoxins and oxidative stress all disrupt the cable-like morphology of functional mitochondria. This results in impaired bioenergetics and mitochondrial migration, and can trigger neurodegeneration. These findings suggest potential new treatment avenues for neurodegenerative diseases.
线粒体是非常动态的细胞器，会发生迁移、分裂和融合。线粒体的分裂和融合循环确保代谢物和线粒体DNA混合，并决定细胞器的形状、数量和生物能量功能。越来越多的证据表明，线粒体功能障碍是神经退行性变的早期因果事件。线粒体融合GTP酶线粒体融合蛋白2和视神经萎缩蛋白1的突变、神经毒素和氧化应激都会破坏功能性线粒体的索状形态。这会导致生物能量学受损和线粒体迁移受阻，并可能引发神经退行性变。这些发现为神经退行性疾病提示了潜在的新治疗途径。
