Glucose-deprivation-triggered aggregation of PUMILIO protein Mpt5 promotes autophagy by inhibiting TOR1 mRNA in Candida albicans

Glucose sensing is essential in organisms ranging from fungi to humans, as the defect results in many cellular abnormalities. While the mechanistic target of rapamycin complex 1 (mTORC1) kinase is a universal sensor and essential regulator for amino acid and nitrogen sensing, little is known about how it monitors glucose. We showed that cells sense glucose deprivation via a PUMILIO-TOR1-autophagy axis, and this mechanism is substantially conserved from fungi to humans. In Candida albicans and human cells, prolonged glucose depletion significantly increases the transcription of PUMILIO RNAs, hence stimulating the development of PUMILIO aggregates via its intrinsically disordered region. These aggregates substantially bind to the 3' untranslated region of TOR1, repressing TOR1 transcripts and activating autophagy. Our studies demonstrated that the PUMILIO-TOR1-autophagy regulatory axis improves fungal tolerance of glucose deprivation. Meanwhile, it adversely regulates hyphal growth and biofilm formation of C. candida, as well as the fitness of the hepatic and renal tissues.