Control of mitochondrial morphology by a human mitofusin.
Control of mitochondrial morphology by a human mitofusin.
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发表时间：
2001-03
影响因子：
4
通讯作者：
A. Santel;M. Fuller
中科院分区：
文献类型：
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作者：
A. Santel;M. Fuller
虽然线粒体大小和排列的变化伴随着细胞分化和人类疾病，但在哺乳动物细胞中介导线粒体融合、分裂和形态发生的机制尚不清楚。我们已经确定了两个人类基因编码线粒体融合的潜在介质。丝裂融合蛋白（Mfn1和Mfn2）是果蝇蛋白质模糊洋葱（Fzo）的同源物，与线粒体相关，并在组织培养细胞中通过瞬时转染表达时改变线粒体形态。包括预测的二分跨膜结构域（TM）的内部区域足以将Mfn2靶向线粒体，并且需要TM内的疏水残基。共同表达Mfn2与显性干扰突变动力蛋白相关蛋白（Drp1（K38A））提出阻止线粒体分裂导致长的线粒体细丝和网络。线粒体细丝和网络的形成需要野生型Mfn2 GTPases结构域，这表明Mfn2 GTPases调节或介导线粒体融合，并且在哺乳动物中，如在酵母中，丝裂融合蛋白和动力蛋白相关的GTP酶在线粒体融合和分裂中发挥相反的作用。
Although changes in mitochondrial size and arrangement accompany both cellular differentiation and human disease, the mechanisms that mediate mitochondrial fusion, fission and morphogenesis in mammalian cells are not understood. We have identified two human genes encoding potential mediators of mitochondrial fusion. The mitofusins (Mfn1 and Mfn2) are homologs of the Drosophila protein fuzzy onion (Fzo) that associate with mitochondria and alter mitochondrial morphology when expressed by transient transfection in tissue culture cells. An internal region including a predicted bipartite transmembrane domain (TM) is sufficient to target Mfn2 to mitochondria and requires hydrophobic residues within the TM. Co-expression of Mfn2 with a dominant interfering mutant dynamin-related protein (Drp1(K38A)) proposed to block mitochondrial fission resulted in long mitochondrial filaments and networks. Formation of mitochondrial filaments and networks required a wild-type Mfn2 GTPase domain, suggesting that the Mfn2 GTPase regulates or mediates mitochondrial fusion and that mitofusins and dynamin related GTPases play opposing roles in mitochondrial fusion and fission in mammals, as in yeast.