Editors' ChoicePosttranslational Modifications

Ferritin out iron with pups

Sci. Signal.  03 May 2016:
Vol. 9, Issue 426, pp. ec103
DOI: 10.1126/scisignal.aag0020

Some bacteria possess a ubiquitin-like protein called Pup (prokaryotic ubiquitin-like protein), which can be covalently attached to target proteins to tag them for proteasomal degradation. However, not all pupylated proteins are degraded, and some bacteria that have pupylation machinery do not have proteasomes, implying that pupylation must have additional roles. Küberl et al. found that pupylation enabled Corynebacterium glutamicum, a bacterium that lacks a proteasome, to adapt to iron-limiting conditions. Although C. glutamicum Δpup mutants grew well on various carbon and nitrogen sources and under conditions of nitrogen stress, these pupylation-defective mutants did not grow as well as wild-type (WT) cells in iron-poor medium. The total cellular iron content, which includes both free and bound iron, was the same in Δpup mutants and WT cells, but the mutant cells had less free iron than WT cells, indicating that iron in the mutant cells was sequestered. Transcriptomic profiling was consistent with hypersensitivity to iron limitation of the Δpup mutants and included increased abundance of transcripts stimulated by low-iron conditions. In WT cells under normal growth conditions, the iron storage protein ferritin (Ftn) was pupylated on Lys78, and mutating this to Ala prevented pupylation of Ftn in WT cells. Under iron-limiting conditions, C. glutamicum Δftn cells expressing this mutant form of Ftn exhibited the same growth defect as Δpup mutants. As expected, pupylation did not cause degradation of Ftn, because the abundance of Ftn did not differ between Δpup and WT C. glutamicum under iron-limiting conditions. Although C. glutamicum lacks a complete proteasome, the proteasomal subunit homolog ARC, which unfolds pupylated proteins, is present, and ARC was required for growth under iron-limiting conditions. Thus, pupylation may enable unfolding of Ftn to release stored iron.

A. Küberl, T. Polen, M. Bott, The pupylation machinery is involved in iron homeostasis by targeting the iron storage protein ferritin. Proc. Natl. Acad. Sci. U.S.A. 113, 4806–4811 (2016). [PubMed]