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New study in Science Advances reveals insights into the regulation of glutathione

September 13, 2023 by Kate Strotmeyer

Research by Yvonne Janssen-Heininger, Ph.D., and Reem Aboushousha, Ph.D, uncovered a novel facet of glutaredoxin, a prominent player in humans’ antioxidant defense system . The findings bear substantial implications in the field of cancer biology.

University Distinguished Professor, Yvonne Janssen-Heininger, PhD and faculty scientist, Reem Aboushousha, PhD

Glutathione, a prominent player in humans’ antioxidant defense system against oxidative stress, is well-recognized in scientific circles. Surprisingly, glutathione can attach itself to proteins and alter their structure and function. This process is known as glutathionylation, and a small helper molecule called glutaredoxin can reverse it.

As published in Science Advances, UVM Cancer Center members, Yvonne Janssen-Heininger, Ph.D., professor of pathology and laboratory medicine, Reem Aboushousha, Ph.D, faculty scientist in the pathology and laboratory medicine department, and colleagues uncovered a novel facet of glutaredoxin. Beyond its role in regulating glutathionylation, the team found that it exerts influence over the levels of glutathione itself. 

This new study delved deeply into the intricate mechanism underpinning this phenomenon, showing how that glutaredoxin disrupts a vital protein complex referred to as System XC-. This complex plays an essential role in importing cystine, a critical precursor required for the synthesis of glutathione. Notably, an escalation in glutathionylation serves as a signal for a component within the System XC- complex, prompting cells to ramp up their production of glutathione.

These findings bear substantial implications, particularly in the field of cancer biology. As tumors upregulate both System XC- and glutathione levels to survive, this study provides empirical evidence of the activation of this pathway in lung cancer. Not only does this research provide new insights into the regulation of glutathione, it also points towards new strategies to intervene.

Related: Probing Oxygen's Mysteries