Abstract
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.
Highlights
Autophagy is a conserved molecular pathway involved in the degradation and recycling of cellular components
PATH2PPI needs to know the homologous relationships between each protein of P. anserina and each protein of human and yeast
Summarizing, we suggest that PaATG8 and its interactions with the conjugation system, consisting of PaATG7, PaATG4, and PaATG3, play a crucial role in the autophagy process in P. anserina as well
Summary
Autophagy is a conserved molecular pathway involved in the degradation and recycling of cellular components. Evidence is emerging that autophagy plays a key role in the degradation of damaged cellular components and thereby affects aging and lifespan control. Different forms of autophagy were detected as major pathways active in recycling during starvation and in molecular quality control (QC). An impaired autophagy system shortens the lifespan of mice [36] or is involved in the development of various age-dependent diseases such as Alzheimer’s, Philipp et al BMC Bioinformatics (2017) 18:196. In yeast treatment with 10, 20, and 40 nM rapamycin extends chronological lifespan This effect is dependent on the presence of ATG1 and ATG7 [2]. Moderate overexpression of Atg results in enhanced autophagy and extends median lifespan by 17% in mice [36]
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