Delineating cysteine catabolism as a mediator of renal stress-resistance

• Applicant: Dr. Felix Köhler
• Subject Area: Nephrology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 578075745

The increasing human life expectancy is one of the most important challenges for modern societies, as age-related diseases are rapidly rising. One of the key organs affected by aging is the kidney. A pivotal problem in aging-associated kidney disease is the elevated risk of acute kidney injury, which is one of the most common diseases in hospitalized patients and is associated with substantial morbidity and mortality. Despite this immense threat to patients, preventive or therapeutic approaches in the clinic are lacking. Specific metabolic changes ameliorated by tailored dietary interventions have recently been identified as underlying mechanisms of organismal resilience. Interestingly, these diets also lead to an increase in cellular and organismal stress-resistance, which makes their medical use in the prevention of kidney damage particularly attractive. In a mouse model of acute kidney injury, we were able to show that different dietary preconditioning strategies are extremely effective in protecting the kidney from ischemic damage. In addition, these beneficial diets commonly induce cysteine catabolism that is considered to be a central mediator of diet-induced kidney protection. The overall aim of the project at hand is to fully delineate the underlying protective molecular mechanisms within cysteine catabolism. Furthermore, we intend to systematically investigate new dietary and pharmacological strategies that modulate the key enzymes of cysteine catabolism with regard to their efficacy in kidney protection. This translational project serves as a basis for the design of future clinical studies on the prevention and treatment of acute kidney injury.

• DFG Programme: Research Grants