Abstract 1109 Initial Identification of MitoNEET as a Transaminase Enzyme

MitoNEET is a [2Fe-2S] redox active mitochondrial protein belonging to the CDGSH iron-sulfur domain (CISD) family of proteins. MitoNEET has been implicated as potential targets for drug development to treat various disorders, including 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. Lys55 is part of the soluble portion of the protein and is in a hydrogen-bonding network with the histidine residue that ligates the [2Fe-2S] cluster. When modified by PLP, mitoNEET catalyzes the transamination reaction of the amino acid cysteine and the alpha-keto acid 2-oxoglutarate to form 3-mercaptopyruvate and glutamate. This work identifies, for the first time, mitoNEET as an enzyme with cysteine transaminase activity. Ongoing work characterizing the substrate specificity and the allosteric modulation of its transaminase activity will be presented. Future studies will be directed towards gaining insight into how mitoNEET is regulating the mitochondrial function, and allow the identification of novel drug-able pathways to modulate mitochondrial function in metabolic diseases. The following support from the NSF supported this work; CHE-160944, CHE-1806266, HRD-1618-408, EES-2308500