Control of a chemical chaperone by a universally conserved ATPase
Hong Jiang,
Martin Milanov,
Gabriela Jüngert,
Larissa Angebauer,
Clara Flender,
Eva Smudde,
Fabian Gather,
Tanja Vogel,
Henning J. Jessen,
Hans-Georg Koch
Affiliations
Hong Jiang
Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; Faculty of Biology, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; Spemann Graduate School of Biology and Medicine, Albert-Ludwigs University Freiburg, 79104 Freiburg, Germany
Martin Milanov
Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; Faculty of Biology, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; Spemann Graduate School of Biology and Medicine, Albert-Ludwigs University Freiburg, 79104 Freiburg, Germany
Gabriela Jüngert
Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany
Larissa Angebauer
Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; Faculty of Biology, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany
Clara Flender
Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany
Eva Smudde
Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany
Fabian Gather
Institute for Anatomy and Cell Biology, Department of Molecular Embryology, Faculty of Medicine, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany
Tanja Vogel
Institute for Anatomy and Cell Biology, Department of Molecular Embryology, Faculty of Medicine, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany
Henning J. Jessen
Institute for Organic Chemistry, Faculty of Chemistry and Pharmacy, University Freiburg 79104 Freiburg, Germany
Hans-Georg Koch
Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; Corresponding author
Summary: The universally conserved YchF/Ola1 ATPases regulate stress response pathways in prokaryotes and eukaryotes. Deletion of YchF/Ola1 leads to increased resistance against environmental stressors, such as reactive oxygen species, while their upregulation is associated with tumorigenesis in humans. The current study shows that in E. coli, the absence of YchF stimulates the synthesis of the alternative sigma factor RpoS by a transcription-independent mechanism. Elevated levels of RpoS then enhance the transcription of major stress-responsive genes. In addition, the deletion of ychF increases the levels of polyphosphate kinase, which in turn boosts the production of the evolutionary conserved and ancient chemical chaperone polyphosphate. This potentially provides a unifying concept for the increased stress resistance in bacteria and eukaryotes upon YchF/Ola1 deletion. Intriguingly, the simultaneous deletion of ychF and the polyphosphate-degrading enzyme exopolyphosphatase causes synthetic lethality in E. coli, demonstrating that polyphosphate production needs to be fine-tuned to prevent toxicity.