Regulating Mitochondrial Metabolism with Itaconate to Mitigate Cerebral Reperfusion Injuries

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Friday, April 10, 2020 -
2:00pm to 3:00pm
Thekla Cordes

Assistant Project Scientist

University of California, San Diego

Regulating Mitochondrial Metabolism with Itaconate to Mitigate Cerebral Reperfusion Injuries


Cerebral ischemia/reperfusion (IR) drives oxidative stress and injurious metabolic processes. However, key-mediators remain unclear, and small molecules, such as itaconate, have emerged as regulators for metabolism and cell function. We investigated the molecular, metabolic, and physiological impact of itaconate treatments to improve metabolic homeostasis and to mitigate reperfusion injuries in in vitro and in vivo model systems. We demonstrated that the “immunometabolite” itaconate slows tricarboxylic acid (TCA) cycle metabolism and buffers redox imbalance in primary brain cells. Addition of itaconate to reperfusion fluids after mouse cerebral IR injury reduced oxidative damage, and inflammation while improving hemodynamics and brain function. Our data indicate that itaconate acts as a mitochondrial modulator to improve physiological outcomes associated with reperfusion injury.


Thekla Cordes is an Assistant Project Scientist at the University of California, San Diego, at the Department of Bioengineering in the group of Christian Metallo. She received her diploma in biotechnology at the University of Braunschweig (Germany) before joining Novartis Biologics (Switzerland) to conduct bioprocess engineering research. She received her Ph.D. from University of Luxembourg, where she studied the metabolism of cancer and inflammation and discovered mammalian itaconate. Cordes was a postdoctoral DFG (German Research Foundation) Fellow at the UCSD. Her current research centers on mammalian metabolism to investigate the impact of mitochondrial dysfunction on health and disease by employing mass spectrometry and tracing approaches.