Control of renal central carbon metabolism by heme oxygenase-1
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 <i>Hmox1</i> deletion model (<i>Hmox1</i> <sup><i>R26Δ/Δ</i></sup> ), we demonstrate that <i>Hmox1</i> 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 <i>Hmox1</i> deletion. This study underscores the critical role of <i>Hmox1</i> for PPP regulation and sheds light on the metabolic pathways involved in kidney dysfunction due to hemolytic diseases.
Authors
- Verena Hoerr (ORCID: https://orcid.org/0000-0002-5301-3636)
- Franziska Röstel
- Gianni Panagiotou (ORCID: https://orcid.org/0000-0001-9393-124X)
- Thorsten Wiech (ORCID: https://orcid.org/0000-0003-4053-1474)
- Marco Groth (ORCID: https://orcid.org/0000-0002-9199-8990)
- Sascha Schäuble (ORCID: https://orcid.org/0000-0003-3862-6546)
- Emma V. King (ORCID: https://orcid.org/0000-0003-0658-1873)
- Wolfgang Vivas
- Gianna Hirth (ORCID: https://orcid.org/0000-0002-5871-5063)
- Elisa Jentho (ORCID: https://orcid.org/0000-0002-4790-7860)
- Miguel P. Soares (ORCID: https://orcid.org/0000-0002-9314-4833)
- Michael Bauer (ORCID: https://orcid.org/0000-0002-1521-3514)
- Sebastian Weis (ORCID: https://orcid.org/0000-0003-3201-2375)
- Joel Guerra (ORCID: https://orcid.org/0000-0002-7149-3784)
- Brendon P. Scicluna (ORCID: https://orcid.org/0000-0003-2826-0341)
- Dania Martínez-Alarcón (ORCID: https://orcid.org/0000-0001-8204-7408)
Institutions
- Universität Hamburg (DE)
- University of Malta (MT)
- University Hospital Bonn (DE)
- Mater Dei Hospital (MT)
- University Medical Center Hamburg-Eppendorf (DE)
- Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
- Jena University Hospital (DE)
- Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
- Instituto Gulbenkian de Ciência (PT)
- Friedrich Schiller University Jena (DE)
- University of Hong Kong (HK)
Publication Details
- Journal
- iScience
- Published
- 2025-12-06
- DOI
- https://doi.org/10.1016/j.isci.2025.114370
- Primary Topic
- Heme Oxygenase-1 and Carbon Monoxide
- Type
- article
- Field-Weighted Citation Impact
- 0.00