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

## TL;DR

This study shows that Hmox1 helps protect the kidneys from failure by regulating a key metabolic pathway during stress.

## Contribution

The study reveals a kidney-specific protective role of Hmox1 in metabolic adaptation through the pentose phosphate pathway.

## Key findings

- Hmox1 is essential for preventing heme-induced kidney failure.
- Hmox1 modulates metabolic stress adaptation via the pentose phosphate pathway.
- Conditional Hmox1 deletion does not affect mouse vigor or lifespan.

## 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 (Hmox1R26Δ/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.

•Conditional deletion of Hmox1 does not impair vigor nor does it reduce lifespan in mice•Hmox1 expression is vital for averting heme-induced acute kidney failure•Hmox1 modulates metabolic stress adaptation via the pentose phosphate pathway•The gene mediates a kidney-specific protective role

Conditional deletion of Hmox1 does not impair vigor nor does it reduce lifespan in mice

Hmox1 expression is vital for averting heme-induced acute kidney failure

Hmox1 modulates metabolic stress adaptation via the pentose phosphate pathway

The gene mediates a kidney-specific protective role

Molecular physiology; Cell biology