The autophagy interaction network of the aging model Podospora anserina

BMC Bioinformatics

Research Article

Ina Koch¹  Oliver Philipp²  Heinz D. Osiewacz³  Andrea Hamann³ 

[1] 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, 60325, Frankfurt am Main, Germany;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, 60325, Frankfurt am Main, 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, 60438, Frankfurt am Main, 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, 60438, Frankfurt am Main, Germany;

关键词: Autophagy;    Aging;    Podospora anserina;    Protein-protein interaction;    ATG8;    Network analysis;    Topological properties;   

DOI  :  10.1186/s12859-017-1603-2

 received in 2016-11-03, accepted in 2017-03-15,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundAutophagy 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.ResultsWe 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.ConclusionsWith 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.

【 授权许可】

CC BY   
© The Author(s) 2017

【 图 表 】

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