Fig 8.

Proposed model for iron sensing by Aft1p. During iron starvation, iron-sulfur assembly in the mitochondria and dimeric Grx3/4p with bound iron-sulfur clusters are minimal. Under these conditions, Grx3/4p binding to Aft1p is attenuated, and Aft1p binds to target promoters to increase the expression of the iron regulon. In response to iron availability (i), iron-sulfur cluster assembly in the mitochondria increases (ii), and the iron-sulfur clusters, or signals that invoke iron-sulfur cluster formation, are delivered to the monothiol glutaredoxins Grx3/4p, which reside in both the nucleus and cytoplasm, via the mitochondrial ABC exporter Atm1p (iii). Grx3/4p with bound iron-sulfur clusters bind to Aft1p (iv), which induces dissociation of Aft1p from its target promoters (v), leaving Aft1p available for nuclear export by Msn5p (vi). The expression of the iron regulon is thereby downregulated.