Mary Konkle
Start: January 23, 2025 3:30 p.m.
End: January 23, 2025 4:30 p.m.

Characterizing the Function/Dysfunction Switch of MitoNEET

Dr. Mary Konkle
Associate Professor, Department of Chemistry, Ball State University

Thursday, 01/23 @ 3:30 PM
FB 253 

MitoNEET, a [2Fe-2S] redox active mitochondrial protein belonging to the CDGSH iron-sulfur domain (CISD) family, has been implicated as a potential targets for drug development to treat various disorders (type-2 diabetes, cancer, and Parkinson’s Disease). However, the specific cellular function(s) for mitoNEET still remains to be fully elucidated, and family presents a significant roadblock in rational drug development. Here we show that mitoNEET binds the enzymatic cofactor pyridoxal phosphate (PLP) specifically at only one of its eleven lysine residues, Lys55. When modified by PLP, mitoNEET catalyzes the transamination of the amino acid cysteine and the alpha-keto acid 2-oxoglutarate to form 3-mercaptopyruvate and glutamate. This work identified, for the first time, mitoNEET as an enzyme with cysteine transaminase activity. The reactive electrophile 4-oxononenal (ONE) was also shown to selectively react with Lys55, also through imine formation. Endogenous ONE production results from oxidative stress and the modification of Lys55 by ONE provided a first mechanistic explanation for how mitoNEET may sense the redox environment of the cell. The selective modification of mitoNEET by PLP or ONE at Lys55 allows for the exciting model that Lys55 is a redox switch that controls function (PLP-bound) and dysfunction (ONE-modified) of the protein.