Department of Infectious Diseases, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
Department of Parasitology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan.
Sci Rep. 2017 Oct 18;7(1):13439. doi: 10.1038/s41598-017-13721-5.
Entamoeba histolytica is an anaerobic parasitic protist and possesses mitosomes, one of the most highly divergent mitochondrion-related organelles (MROs). Although unique metabolism and protein/metabolite transport machinery have been demonstrated in Entamoeba mitosomes, the mechanism of mitosomal fusion and fission remains to be elucidated. In this study, we demonstrate that two dynamin-related proteins (DRPs) are cooperatively involved in the fission of Entamoeba mitosomes. Expression of a dominant negative form of EhDrpA and EhDrpB, and alternatively, repression of gene expression of EhDrpA and EhDrpB genes, caused elongation of mitosomes, reflecting inhibition of mitosomal fission. Moreover, EhDrpA and EhDrpB formed an unprecedented hetero-oligomeric complex with an approximate 1:2 to 1:3 ratio, suggesting that the observed elongation of mitosomes is likely caused by the disruption and instability of the complex caused by an imbalance in the two DRPs. Altogether, this is the first report of a hetero-oligomeric DRP complex which participates in the fission of mitochondria and MROs.
溶组织内阿米巴是一种厌氧寄生原生动物，具有线粒体相关细胞器（MROs）中分化程度最高的类线粒体。虽然在溶组织内阿米巴的线粒体中已经证明了独特的代谢和蛋白质/代谢物转运机制，但线粒体融合和裂变的机制仍有待阐明。在这项研究中，我们证明了两种与动力蛋白相关的蛋白（DRPs）协同参与溶组织内阿米巴线粒体的裂变。表达显性负形式的 EhDrpA 和 EhDrpB，或者替换性地抑制 EhDrpA 和 EhDrpB 基因的表达，导致线粒体伸长，反映了线粒体裂变的抑制。此外，EhDrpA 和 EhDrpB 形成了一种前所未有的异源寡聚复合物，其比例约为 1:2 至 1:3，这表明观察到的线粒体伸长可能是由于两种 DRPs 失衡导致复合物的破坏和不稳定性所致。总之，这是第一个报道参与线粒体和 MRO 裂变的异源寡聚 DRP 复合物的报告。
