The Metabolic Regulation of the TOR Pathway and the Circadian Rhythmicity of Neurospora crassa

Eukaryotic circadian rhythms are often attributed to transcription-translation feedback loops (TTFLs). However, rhythms can still persist in the absence of functioning TTFLs. Our laboratory has discovered that mutations in the components of the TOR pathway compromise the non- TTFL rhythms, implying the potential involvement of this pathway in regulating the rhythmicity of Neurospora crassa.

The TOR pathway is a nutrient-sensing pathway that its modulation in Neurospora remains enigmatic. Here, I investigated the metabolic regulation of the TOR pathway to delineate its relationship with circadian rhythmicity. Using the phosphorylation state of S6 ribosomal protein, I found that different metabolites, including amino acids and lipids affect the TOR pathway only after a prolonged glucose-starvation period, suggesting that glucose alone is sufficient to activate the TOR pathway. Interestingly, my findings indicate that factors perturbing the TOR activity also influence the period of conidiation, thereby establishing a connection between the TOR pathway and circadian rhythmicity.