Depletion of Mitochondrial Acyl Carrier Protein in Bloodstream-Form Trypanosoma brucei Causes a Kinetoplast Segregation Defect
Depletion of Mitochondrial Acyl Carrier Protein in Bloodstream-Form Trypanosoma brucei Causes a Kinetoplast Segregation Defect
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DOI：
10.1128/ec.00290-10
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发表时间：
2011-03-01
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影响因子：
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通讯作者：
Englund, Paul T.
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文献类型：
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作者：
Clayton, April M.;Guler, Jennifer L.;Englund, Paul T.
像其他真核生物一样，锥虫在线粒体中有一个必需的II型脂肪酸合成酶。我们通过研究条件敲除酰基载体蛋白（ACP）的作用，研究了这种合成酶在血流型寄生虫中的功能，ACP是这种脂肪酸合成酶途径的关键参与者。我们发现ACP耗竭不仅引起细胞磷脂的微小变化，而且令人惊讶的是，引起了着丝体的变化。这种结构包含了由数千个互锁DNA环组成的巨大网络形式的线粒体基因组（着丝质体DNA [kDNA]），在一些细胞中变大，而在另一些细胞中变小或不存在。我们在荧光或电子显微镜观察的孤立网络中观察到相同的模式。我们发现kDNA大小的变化不是由于复制的中断，而是由于分离的缺陷。kDNA分离是由三方附着复合体（TAC）介导的，我们假设当ACP被耗尽时，TAC成分之一（线粒体双膜的分化区域）的磷脂组成发生了改变。我们进一步推测这种成分变化会影响TAC功能，从而影响kDNA的分离。
Like other eukaryotes, trypanosomes have an essential type II fatty acid synthase in their mitochondrion. We have investigated the function of this synthase in bloodstream-form parasites by studying the effect of a conditional knockout of acyl carrier protein (ACP), a key player in this fatty acid synthase pathway. We found that ACP depletion not only caused small changes in cellular phospholipids but also, surprisingly, caused changes in the kinetoplast. This structure, which contains the mitochondrial genome in the form of a giant network of several thousand interlocked DNA rings (kinetoplast DNA [kDNA]), became larger in some cells and smaller or absent in others. We observed the same pattern in isolated networks viewed by either fluorescence or electron microscopy. We found that the changes in kDNA size were not due to the disruption of replication but, instead, to a defect in segregation. kDNA segregation is mediated by the tripartite attachment complex (TAC), and we hypothesize that one of the TAC components, a differentiated region of the mitochondrial double membrane, has an altered phospholipid composition when ACP is depleted. We further speculate that this compositional change affects TAC function, and thus kDNA segregation.