IMC10 and LMF1 mediate mitochondrial morphology through mitochondrion-pellicle contact sites in Toxoplasma gondii.
IMC10 and LMF1 mediate mitochondrial morphology through mitochondrion-pellicle contact sites in Toxoplasma gondii.
复制标题
DOI：
10.1242/jcs.260083
复制
发表时间：
2022-11-15
影响因子：
4
通讯作者：
中科院分区：
文献类型：
--
作者：
弓形虫的单个线粒体是高度动态的，在细胞内寄生虫中主要呈外周分布的套索形状，而在细胞外寄生虫中则塌陷。线粒体的外周定位与线粒体膜和寄生虫表膜之间的明显接触有关。线粒体外膜相关蛋白 LMF1 对于线粒体的正确定位至关重要。缺乏 LMF1 的细胞内寄生虫无法形成套索状线粒体。为了鉴定将寄生虫的线粒体束缚在表膜上的其他蛋白质，我们对 LMF1 相互作用子进行了酵母双杂交筛选。我们鉴定了 70 个位于不同细胞区室的假定相互作用因子，例如寄生虫的顶端、线粒体膜和内膜复合物 (IMC)，包括薄膜蛋白 IMC10。通过蛋白质-蛋白质相互作用测定，我们证实了 LMF1 与 IMC10 的相互作用。 IMC10 的条件性敲除不会影响寄生虫的活力，但会严重影响细胞内寄生虫的线粒体形态以及分裂过程中线粒体向子细胞的分布。实际上，IMC10 敲低会破坏 LMF1 的表型，表明这两种蛋白在弓形虫线粒体和 IMC 之间定义了一种新型膜系链。 。摘要：由 LMF1 和 IMC10 组成的束缚复合物强调了表膜-线粒体膜接触位点在维持弓形虫细胞器形态和分布方面的重要性。
The single mitochondrion of Toxoplasma gondii is highly dynamic, being predominantly in a peripherally distributed lasso-shape in intracellular parasites and collapsed in extracellular parasites. The peripheral positioning of the mitochondrion is associated with apparent contacts between the mitochondrion membrane and the parasite pellicle. The outer mitochondrial membrane-associated protein LMF1 is critical for the correct positioning of the mitochondrion. Intracellular parasites lacking LMF1 fail to form the lasso-shaped mitochondrion. To identify other proteins that tether the mitochondrion of the parasite to the pellicle, we performed a yeast two-hybrid screen for LMF1 interactors. We identified 70 putative interactors localized in different cellular compartments, such as the apical end of the parasite, mitochondrial membrane and the inner membrane complex (IMC), including with the pellicle protein IMC10. Using protein–protein interaction assays, we confirmed the interaction of LMF1 with IMC10. Conditional knockdown of IMC10 does not affect parasite viability but severely affects mitochondrial morphology in intracellular parasites and mitochondrial distribution to the daughter cells during division. In effect, IMC10 knockdown phenocopies disruption of LMF1, suggesting that these two proteins define a novel membrane tether between the mitochondrion and the IMC in Toxoplasma. . Summary: A tethering complex composed by LMF1 and IMC10 highlights the importance of pellicle–mitochondrion membrane contact sites in maintaining organelle morphology and distribution in Toxoplasma gondii.
登录
查看更多内容
影响因子：
3.7
作者：
Guzmán C;Bagga M;Kaur A;Westermarck J;Abankwa D
通讯作者：
Abankwa D
影响因子：
3.7
作者：
Behnke MS;Wootton JC;Lehmann MM;Radke JB;Lucas O;Nawas J;Sibley LD;White MW
通讯作者：
White MW
影响因子：
6.4
作者：
Chen AL;Kim EW;Toh JY;Vashisht AA;Rashoff AQ;Van C;Huang AS;Moon AS;Bell HN;Bentolila LA;Wohlschlegel JA;Bradley PJ
通讯作者：
Bradley PJ
影响因子：
3.6
作者：
Heredero-Bermejo I;Varberg JM;Charvat R;Jacobs K;Garbuz T;Sullivan WJ Jr;Arrizabalaga G
通讯作者：
Arrizabalaga G
影响因子：
1.5
作者：
Gubbels, MJ;Wieffer, M;Striepen, B
通讯作者：
Striepen, B