Ribosomal Protein Mutations Induce Autophagy through S6 Kinase Inhibition of the Insulin Pathway

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Diseases linked to mutations affecting the ribosome, ribosomopathies, have an exceptionally wide range of phenotypes. However, many ribosomopathies have some features in common including cytopenia and growth defects. Our study aims to clarify the mechanisms behind these common phenotypes. We find that mutations in ribosomal protein genes result in a series of aberrant signaling events that cause cells to start recycling and consuming their own intracellular contents. This basic mechanism of catabolism is activated when cells are starving for nutrients, and also during the tightly regulated process of blood cell maturation. The deregulation of this mechanism provides an explanation as to why blood cells are so acutely affected by mutations in genes that impair the ribosome. Moreover, we find that the signals activating this catabolism are coupled to impairment of the highly conserved insulin-signaling pathway that is essential for growth. Taken together, our in-depth description of the pathways involved as the result of mutations affecting the ribosome increases our understanding about the etiology of these diseases and opens up previously unknown avenues of potential treatment.

Vyšlo v časopise: Ribosomal Protein Mutations Induce Autophagy through S6 Kinase Inhibition of the Insulin Pathway. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004371
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004371

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