Casting iron into the cell fate mold

This commentary discusses general concepts introduced in the article 'Bulk autophagy induction and life extension is achieved when iron is the only limited nutrient in Saccharomyces cerevisiae' by Montella-Manuel et al. (Biochem J (2021) 478: 811-837). Montella-Manuel et al. show that like central carbon metabolism, iron metabolism is also closely implicated in autophagy-mediated life extension via the TORC2 activator Ypk1p and the iron regulator Aft1p. While not being an iron-sulfur cluster protein, Aft1p interacts with such proteins and thus senses the redox status of the cell, which, similar to amino acids and AMP, reports its energetic status. Furthermore, glucose and iron deficiencies are interrelated as the diauxic shift in glucose depleted cells requires iron uptake for activating respiration in the absence of fermentation.