SGK-1 mediated inhibition of iron import is a determinant of lifespan in C. elegans

Maintaining iron levels is crucial for health, but iron overload has been associated with tumorigenesis. Therefore, critical enzymes involved in iron homeostasis are under tight, typically posttranslational control. In C. elegans , the mTORC2 and insulin/IGF-1 activated kinase SGK-1 is induced upon exogenous iron overload to couple iron storage and fat accumulation. Here we show that, already at physiological iron conditions, sgk-1 loss-of-function increases intracellular iron levels that may impair lifespan. Reducing iron levels by diminishing cellular or mitochondrial iron import is sufficient to extend the short lifespan of sgk-1 loss-of-function animals. Our results indicate another regulatory level of sgk-1 in iron homeostasis via negative feedback regulation on iron transporters.