Philipp Oliver, Hamann Andrea, Osiewacz Heinz D, Koch Ina
Molecular Bioinformatics, Institute of Computer Science, Faculty of Computer Science and Mathematics and Cluster of Excellence 'Macromolecular Complexes', Johann Wolfgang Goethe-University Frankfurt am Main, Robert-Mayer-Str. 11-15, Frankfurt am Main, 60325, Germany.
Molecular Developmental Biology, Institute of Molecular Biosciences, Faculty for Biosciences & Cluster of Excellence 'Macromolecular Complexes', Johann Wolfgang Goethe-University Frankfurt am Main, Max-von-Laue-Str. 9, Frankfurt am Main, 60438, Germany.
BMC Bioinformatics. 2017 Mar 27;18(1):196. doi: 10.1186/s12859-017-1603-2.
Autophagy is a conserved molecular pathway involved in the degradation and recycling of cellular components. It is active either as response to starvation or molecular damage. Evidence is emerging that autophagy plays a key role in the degradation of damaged cellular components and thereby affects aging and lifespan control. In earlier studies, it was found that autophagy in the aging model Podospora anserina acts as a longevity assurance mechanism. However, only little is known about the individual components controlling autophagy in this aging model. Here, we report a biochemical and bioinformatics study to detect the protein-protein interaction (PPI) network of P. anserina combining experimental and theoretical methods.
We constructed the PPI network of autophagy in P. anserina based on the corresponding networks of yeast and human. We integrated PaATG8 interaction partners identified in an own yeast two-hybrid analysis using ATG8 of P. anserina as bait. Additionally, we included age-dependent transcriptome data. The resulting network consists of 89 proteins involved in 186 interactions. We applied bioinformatics approaches to analyze the network topology and to prove that the network is not random, but exhibits biologically meaningful properties. We identified hub proteins which play an essential role in the network as well as seven putative sub-pathways, and interactions which are likely to be evolutionary conserved amongst species. We confirmed that autophagy-associated genes are significantly often up-regulated and co-expressed during aging of P. anserina.
With the present study, we provide a comprehensive biological network of the autophagy pathway in P. anserina comprising PPI and gene expression data. It is based on computational prediction as well as experimental data. We identified sub-pathways, important hub proteins, and evolutionary conserved interactions. The network clearly illustrates the relation of autophagy to aging processes and enables further specific studies to understand autophagy and aging in P. anserina as well as in other systems.
自噬是一种保守的分子途径，参与细胞成分的降解和循环利用。它在对饥饿或分子损伤的反应中发挥作用。越来越多的证据表明，自噬在受损细胞成分的降解中起关键作用，从而影响衰老和寿命控制。在早期研究中，发现衰老模型嗜热栖热放线菌中的自噬作为一种寿命保证机制。然而，对于该衰老模型中控制自噬的单个成分知之甚少。在此，我们报告一项生化和生物信息学研究，结合实验和理论方法来检测嗜热栖热放线菌的蛋白质-蛋白质相互作用（PPI）网络。
我们基于酵母和人类的相应网络构建了嗜热栖热放线菌自噬的PPI网络。我们整合了在以嗜热栖热放线菌的ATG8为诱饵的酵母双杂交分析中鉴定出的PaATG8相互作用伙伴。此外，我们纳入了年龄依赖性转录组数据。所得网络由89种蛋白质组成，涉及186种相互作用。我们应用生物信息学方法分析网络拓扑结构，并证明该网络并非随机的，而是具有生物学意义的特性。我们鉴定出在网络中起关键作用的枢纽蛋白以及七个假定的子途径，以及可能在物种间进化保守的相互作用。我们证实自噬相关基因在嗜热栖热放线菌衰老过程中经常显著上调并共同表达。
通过本研究，我们提供了一个包含PPI和基因表达数据的嗜热栖热放线菌自噬途径的全面生物学网络。它基于计算预测以及实验数据。我们鉴定出子途径、重要的枢纽蛋白以及进化保守的相互作用。该网络清楚地阐明了自噬与衰老过程的关系，并有助于开展进一步的具体研究，以了解嗜热栖热放线菌以及其他系统中的自噬和衰老。
