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首页> 外文会议>IEEE Conference on Computational Intelligence in Bioinformatics and Computational Biology >In SILICO Simulations Predict a Causative Link Between Increased Glycolysis and Metabolic Reprogramming in Autosomal Dominant Polycystic Kidney Disease
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In SILICO Simulations Predict a Causative Link Between Increased Glycolysis and Metabolic Reprogramming in Autosomal Dominant Polycystic Kidney Disease

机译：在SILICO模拟中，预测了常染色体显性多囊肾疾病中糖酵解增加和代谢重编程之间的因果关系

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Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder characterized by bilateral renal cyst formation due to loss-of-functions mutations in either PKD1 or PKD2 genes. Metabolic rewiring is an important feature of the disease. In this work, we merged biological knowledge and computational modelling to simulate the metabolic changes of bioenergetic pathways that we observed in ADPKD in a previous study, i.e. increased glucose uptake, increased mitochondrial glutamine uptake, increased fatty acids synthesis and reduced fatty acids oxidation. We found that the simulations of each of these alterations result in shared important overall metabolic changes in similar pathways. However, only increased glycolysis recapitulates simultaneously all changes observed in $Pkd1^{-/-}$ cells, while each of the other simulations caused multiple changes, but did not recapitulate the entire picture. Finally, we proved that citrate has a central role in modulating the switch toward alternative bioenergetic pathways, and we speculate that this metabolite is one of the key factors for the metabolic alterations observed in ADPKD.
机译：常染色体显性多囊肾病（ADPKD）是一种遗传性疾病，其特征是由于PKD1或PKD2基因的功能丧失突变导致双侧肾囊肿形成。代谢重新布线是该疾病的重要特征。在这项工作中，我们结合了生物学知识和计算模型来模拟在先前研究中在ADPKD中观察到的生物能途径的代谢变化，即增加葡萄糖摄取，增加线粒体谷氨酰胺摄取，增加脂肪酸合成并减少脂肪酸氧化。我们发现，这些改变中的每一个的模拟导致相似途径中共有重要的整体代谢变化。但是，只有糖酵解的增加才能同时概括在糖酵解中观察到的所有变化。 $ Pkd1 ^ {-/- } $ 单元，而其他每个模拟都引起了多次更改，但没有概括整个图片。最后，我们证明了柠檬酸盐在调节向其他生物能途径的转换中起着核心作用，并且我们推测这种代谢物是在ADPKD中观察到的代谢改变的关键因素之一。

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