Non-dikarya fungi share the TORC1 pathway with animals, not with Saccharomyces cerevisiae

Abstract

Target of rapamycin (TOR), discovered in Saccharomyces cerevisiae, is a highly conserved serine/threonine kinase acting as a regulatory hub between the cell and its environment. Like mammals, in fungi, the TOR complex 1 (TORC1) pathway is essential for coordinating cell growth in response to nutrient availability. The activation of TORC1 is similar in yeast and mammals, while its inhibition is more complex in mammals. This divergence of TORC1 regulation opens the question of how common are the yeast and mammalian variants in the fungal kingdom. In this work, we trace the evolutionary history of TORC1 components throughout the fungal kingdom. Our findings show that these fungi contain the mammalian-specific KICSTOR complex for TORC1 inhibition. They also possess orthologs of serine, arginine and methionine sensors of TORC1 pathway that orchestrate the response to nutrient starvation in mammals. The Rheb-TSC mediated activation of mammalian TORC1 that was lost in Saccharomycotina was also conserved in non-Dikarya. These findings indicate that the TORC1 pathway in non-Dikarya fungi resembles mammalian TORC1. Saccharomycotina lost many of the inhibitory components and evolved alternate regulatory mechanisms. Furthermore, our work highlights the limitations of using S. cerevisiae as a fungal model while putting forward other fungi as possible research models.