title: The pupylation machinery is involved in iron homeostasis by targeting the iron storage protein ferritin.
abstract: The balance of sufficient iron supply and avoidance of iron toxicity by iron homeostasis is a prerequisite for cellular metabolism and growth. Here we provide evidence that, in Actinobacteria, pupylation plays a crucial role in this process. Pupylation is a posttranslational modification in which the prokaryotic ubiquitin-like protein Pup is covalently attached to a lysine residue in target proteins, thus resembling ubiquitination in eukaryotes. Pupylated proteins are recognized and unfolded by a dedicated AAA+ ATPase (Mycobacterium proteasomal AAA+ ATPase; ATPase forming ring-shaped complexes). In Mycobacteria, degradation of pupylated proteins by the proteasome serves as a protection mechanism against several stress conditions. Other bacterial genera capable of pupylation such as Corynebacterium lack a proteasome, and the fate of pupylated proteins is unknown. We discovered that Corynebacterium glutamicum mutants lacking components of the pupylation machinery show a strong growth defect under iron limitation, which was caused by the absence of pupylation and unfolding of the iron storage protein ferritin. Genetic and biochemical data support a model in which the pupylation machinery is responsible for iron release from ferritin independent of degradation.
authors.affiliation: IBG-1: Biotechnology, Institute of Bio- and Geosciences, Forschungszentrum Jülich, 52425 Juelich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Küberl
authors.affiliation: IBG-1: Biotechnology, Institute of Bio- and Geosciences, Forschungszentrum Jülich, 52425 Juelich, Germany t.polen@fz-juelich.de m.bott@fz-juelich.de.
authors.forename: Tino
authors.initials: T
authors.lastname: Polen
authors.affiliation: IBG-1: Biotechnology, Institute of Bio- and Geosciences, Forschungszentrum Jülich, 52425 Juelich, Germany t.polen@fz-juelich.de m.bott@fz-juelich.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Bott
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D003352:Corynebacterium / Q000378:metabolism*; D005293:Ferritins / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D007501:Iron / Q000378:metabolism*; D008954:Models, Biological; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D005293:Ferritins; D007501:Iron; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases
keywords: ATPase ARC; Corynebacterium; Mycobacterium; iron limitation; prokaryotic ubiquitin-like protein