title: Starvation-response may not involve Atg1-dependent autophagy induction in non-unikont parasites.
abstract: Autophagy, the lysosome-mediated self-degradation process, is implicated in survival during starvation in yeast, Dictyostelium and animals. In these eukaryotic taxa (collectively called Unikonts), autophagy is induced primarily through the Atg1/ULK1 complex in response to nutrient depletion. Autophagy has also been well-studied in non-unikont parasites, such as Trypanosoma and Plasmodium, and found important in their life-cycle transitions. However, how autophagy is induced in non-unikonts remains largely unrevealed. Using a bioinformatics approach, we examined the presence of Atg1 and of its complex in the genomes of 40 non-unikonts. We found that these genomes do not encode typical Atg1 proteins: BLAST and HMMER queries matched only with the kinase domain of Atg1, while other segments responsible for regulation and protein-binding were missing. Non-unikonts also lacked other components of the Atg1-inducing complex. Orthologs of an alternative autophagy inducer, Atg6 were found only in the half of the species, indicating that the other half may possess other inducing mechanisms. As key autophagy genes have differential expression patterns during life-cycle, we raise the possibility that autophagy in these protists is induced mainly at the post-transcriptional level. Understanding Atg1-independent autophagy induction mechanisms in these parasites may lead to novel pharmacological interventions, not affecting human Atg1-dependent autophagy.
authors: Department of Genetics, Eötvös Loránd University, Budapest, Hungary.
authors: László
authors: L
authors: Földvári-Nagy
authors: Department of Genetics, Eötvös Loránd University, Budapest, Hungary.
authors: Eszter
authors: E
authors: Ari
authors: Department of Medical Chemistry, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
authors: Péter
authors: P
authors: Csermely
authors: 1] Department of Genetics, Eötvös Loránd University, Budapest, Hungary [2] TGAC, The Genome Analysis Centre, Norwich, UK [3] Gut Health and Food Safety Programme, Institute of Food Research, Norwich, UK.
authors: Tamás
authors: T
authors: Korcsmáros
authors: Department of Genetics, Eötvös Loránd University, Budapest, Hungary.
authors: Tibor
authors: T
authors: Vellai
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D019295:Computational Biology; D030541:Databases, Genetic; D010802:Phylogeny; D010961:Plasmodium / Q000145:classification / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013217:Starvation; D014345:Trypanosoma / Q000145:classification / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015800:Protozoan Proteins; D029701:Saccharomyces cerevisiae Proteins; D017346:Protein Serine-Threonine Kinases