Physiological functions of mitochondrial fusion
Physiological functions of mitochondrial fusion
复制标题
DOI：
10.1111/j.1749-6632.2010.05615.x
复制
发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Chan, David C.
中科院分区：
文献类型：
--
作者：
Chen, Hsiuchen;Chan, David C.
近年来，线粒体的动态性质已被发现对其功能至关重要。在这里，我们讨论线粒体融合的分子基础，其在神经退行性变中的保护作用，以及其在细胞功能中的重要性。线粒体融合蛋白Mfn1和Mfn2，定位于外膜的GTP酶，介导外膜融合。OPA 1是一种与内膜相关的GT3，介导随后的内膜融合。Mfn2或OPA1的突变导致神经退行性疾病。具有线粒体融合基因缺陷的小鼠模型为理解融合如何维持线粒体生理学和神经元功能提供了重要途径。线粒体融合使线粒体群体内的内容物能够混合，从而防止必需成分的永久损失。因此，线粒体融合减少的细胞显示出缺乏mtDNA类核的线粒体亚群。这种mtDNA缺陷导致呼吸缺陷型线粒体，它们在神经元中的积累导致细胞过程的生长受损，最终导致神经退行性变。
In recent years, the dynamic nature of mitochondria has been discovered to be critical for their function. Here we discuss the molecular basis of mitochondrial fusion, its protective role in neurodegeneration, and its importance in cellular function. The mitofusins Mfn1 and Mfn2, GTPases localized to the outer membrane, mediate outermembrane fusion. OPA1, a GTPase associated with the inner membrane, mediates subsequent inner-membrane fusion. Mutations in Mfn2 or OPA1 cause neurodegenerative diseases. Mouse models with defects in mitochondrial fusion genes have provided important avenues for understanding how fusion maintains mitochondrial physiology and neuronal function. Mitochondrial fusion enables content mixing within a mitochondrial population, thereby preventing permanent loss of essential components. Cells with reduced mitochondrial fusion, as a consequence, show a subpopulation of mitochondria that lack mtDNA nucleoids. Such mtDNA defects lead to respiration-deficient mitochondria, and their accumulation in neurons leads to impaired outgrowth of cellular processes and ultimately neurodegeneration.