Depletion of Toxoplasma adenine nucleotide translocator leads to defects in mitochondrial morphology.
Depletion of Toxoplasma adenine nucleotide translocator leads to defects in mitochondrial morphology.
复制标题
弓形虫腺嘌呤核苷酸易位子的消耗导致线粒体形态缺陷
DOI：
10.1186/s13071-022-05295-7
复制
发表时间：
2022-05-31
影响因子：
3.2
通讯作者：
中科院分区：
文献类型：
--
作者：
背景
腺嘌呤核苷酸转位酶（ANT）是催化ADP/ATP跨线粒体内膜交换的蛋白质。除此之外，ANT与细胞死亡途径和线粒体功能障碍密切相关。它是许多疾病的潜在治疗靶点。ANT在弓形虫中的功能知之甚少。
方法
利用CRISPR/CAS9基因编辑工具对T.刚地。我们构建了T。目的：研究弓形虫ANT转基因株系，包括内源性标签株、基因敲除株和基因互补株，以阐明TgANT的功能和定位。免疫荧光和透射电镜观察线粒体形态。
结果
弓形虫编码一种ANT蛋白，命名为TgANT。TgANT定位于线粒体内膜。Δant菌株的增殖显著降低。更重要的是，TgANT的耗尽导致线粒体的形态和超微结构的显着变化，异常顶质体分裂和异常的细胞骨架的子出芽。此外，Δant菌株对小鼠的致病性也明显降低。
结论
总之，我们鉴定并表征了T.刚地。耗尽TgANT抑制寄生虫的生长和受损的顶质体和线粒体生物合成，以及异常的寄生虫分裂，表明TgANT是重要的寄生虫的生长。
Background
Adenine nucleotide translocase (ANT) is a protein that catalyzes the exchange of ADP/ATP across the inner mitochondrial membrane. Beyond this, ANT is closely associated with cell death pathways and mitochondrial dysfunction. It is a potential therapeutic target for many diseases. The function of the ANT in Toxoplasma gondii is poorly understood.
Methods
The CRISPR/CAS9 gene editing tool was used to identify and study the function of the ANT protein in T. gondii. We constructed T. gondii ANT transgenic parasite lines, including endogenous tag strain, knockout strain and gene complement strain, to clarify the function and location of TgANT. Mitochondrial morphology was observed by immunofluorescence and transmission electron microscopy.
Results
Toxoplasma gondii was found to encode an ANT protein, which was designated TgANT. TgANT localized to the inner mitochondrial membrane. The proliferation of the Δant strain was significantly reduced. More important, depletion of TgANT resulted in significant changes in the morphology and ultrastructure of mitochondria, abnormal apicoplast division and abnormal cytoskeletal daughter budding. In addition, the pathogenicity of the Δant strain to mice was significantly reduced.
Conclusions
Altogether, we identified and characterized the ANT protein of T. gondii. Depletion of TgANT inhibited parasite growth and impaired apicoplast and mitochondrial biogenesis, as well as abnormal parasite division, suggesting TgANT is important for parasite growth.
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DOI：
10.1016/s0167-5699(05)80006-4
发表时间：
1991-03-01
期刊：
IMMUNOPARASITOLOGY TODAY-A COMBINED ISSUE OF IMMUNOLOGY TODAY AND PARASITOLOGY TODAY
影响因子：
--
作者：
LIEW, FY;COX, FEG
通讯作者：
COX, FEG
影响因子：
5.4
作者：
Sheiner L;Vaidya AB;McFadden GI
通讯作者：
McFadden GI
DOI：
10.1111/jeu.12906
发表时间：
2022-11
期刊：
The Journal of eukaryotic microbiology
影响因子：
--
作者：
通讯作者：
--
弓形虫酰基辅酶 A 结合蛋白 TgACBP2 的综合表征及其在寄生虫心磷脂代谢中的关键作用
影响因子：
6.4
作者：
Fu Y;Cui X;Fan S;Liu J;Zhang X;Wu Y;Liu Q
通讯作者：
Liu Q
影响因子：
0.8
作者：
Brown, Kevin M.;Long, Shaojun;Sibley, L. David
通讯作者：
Sibley, L. David