System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Epublish

PubMed: 41550715 DOI: 10.1016/j.isci.2025.114370

Control of renal central carbon metabolism by heme oxygenase-1.

iScience 29(1):114370

Authors: Joel Guerra, Elisa Jentho, Sascha Schäuble, Brendon P Scicluna, Wolfgang Vivas, Dania Martínez-Alarcón, Marco Groth, Emma King, Franziska Röstel, Gianna Hirth, Miguel P Soares, Thorsten Wiech, Gianni Panagiotou, Michael Bauer, Verena Hoerr, Sebastian Weis

Affiliations

  • Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Friedrich-Schiller University, Jena, Germany. Center for Sepsis Control and Care, Jena University Hospital, Friedrich-Schiller University, Jena, Germany.
  • Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Friedrich-Schiller University, Jena, Germany.
  • Gulbenkian Institute for Molecular Medicine, Lisboa, Portugal.
  • Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll Institute (Leibniz-HKI), Jena, Germany.
  • Department of Applied Biomedical Science, Faculty of Health Sciences, Mater Dei Hospital, University of Malta, Msida, Malta.
  • Centre for Molecular Medicine and Biobanking, Biomedical Sciences, University of Malta, Msida, Malta.
  • Institute for Infectious Disease and Infection Control, Jena University Hospital, Friedrich-Schiller University, Jena, Germany.
  • Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll Institute- HKI, Jena, Germany.
  • Institute for Infectious Disease and Infection Control, Jena University Hospital, Friedrich-Schiller University, Jena, Germany. Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll Institute- HKI, Jena, Germany.
  • Genome Analysis, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, Germany.
  • Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Friedrich-Schiller University, Jena, Germany. Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll Institute- HKI, Jena, Germany.
  • Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Department of Medicine and State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong, China.
  • Friedrich Schiller University, Faculty of Biological Sciences, Jena, Germany.
  • Center for Sepsis Control and Care, Jena University Hospital, Friedrich-Schiller University, Jena, Germany.
  • Institute of Medical Microbiology, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany.
  • Heart Center Bonn, Department of Internal Medicine II, University Hospital Bonn, Bonn, Germany.

Abstract

Metabolic adaptation is an integral part of the organismal stress-response. In this study, we investigate the role of Hmox1 in mediating metabolic adaptation under both physiological and hemolytic stress conditions. Using an inducible Hmox1 deletion model (Hmox1 R26Δ/Δ ), we demonstrate that Hmox1 expression is essential for preventing heme-induced kidney failure. Our integrative approach, combining bulk RNA sequencing and targeted metabolomics within silico metabolic modeling, revealed a compromised pentose phosphate pathway (PPP) in failed renal adaptation after Hmox1 deletion. This study underscores the critical role of Hmox1 for PPP regulation and sheds light on the metabolic pathways involved in kidney dysfunction due to hemolytic diseases.

MeSH

Heme Oxygenase-1, Stress, Physiological, Oxygenases, Kidney, Heme, Heme Oxygenase (Decyclizing)