RT Journal Article SR Electronic T1 Ferrosomes are iron storage organelles formed by broadly conserved gene clusters in bacteria and archaea JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.01.10.902569 DO 10.1101/2020.01.10.902569 A1 Carly R. Grant A1 Arash Komeili YR 2020 UL http://biorxiv.org/content/early/2020/01/11/2020.01.10.902569.abstract AB Cellular iron homeostasis is vital and maintained through tight regulation of iron import, efflux, storage, and detoxification1–3. The most common modes of iron storage employ proteinaceous compartments that are composed of ferritin or related proteins4,5. While lipid-bounded iron compartments have also been described, the basis for their formation and function remains unknown. Here, we focus on one such compartment, the ferrosome, which had been previously observed in the anaerobic bacterium Desulfovibrio magneticus6. We identify three ferrosome-associated (Fez) proteins, encoded by a putative operon, that are associated with and responsible for forming ferrosomes in D. magneticus. Fez proteins include FezB, a P1B-6-ATPase found in phylogenetically and metabolically diverse species of bacteria and archaea with anaerobic lifestyles. In the majority of these species, two to ten genes define a cluster that encodes FezB. We show that two other species, Rhodopseudomonas palustris and Shewanella putrefaciens, make ferrosomes in anaerobic conditions through the action of their six-gene fez operon. Additionally, we find that the S. putrefaciens fez operon is sufficient for ferrosome formation in Escherichia coli. Using S. putrefaciens as a model, we find that ferrosomes likely play a role in the anaerobic adaptation to iron starvation. Overall, this work establishes ferrosomes as a new class of lipid-bounded iron storage organelles and sets the stage for studying ferrosome formation and structure in diverse microorganisms.