Subsequence searching also identified a proteolytic cleavage site in CDGSH iron-sulfur domaincontaining protein 1 (mitoNEET, Q9NZ45) at L47 (Figure ). MitoNEET is a mitochondrial outermembrane protein that was initially discovered as an off-target interactor of the PPAR-γ agonist pioglitazone. With its iron-sulfur cluster oriented toward the cytosol, mitoNEET acts as a redox sensor and regulator of mitochondrial iron. Downregulation of mitNEET has been associated with aging and increased risk of heart failure. The canonical proteoform of mitoNEET was observed in both small intestine and heart tissue, while both proteolytic products were observed solely in heart tissue (Figure ). Cleavage at L47 does not disrupt the iron-sulfur cluster binding site but does separate this reactive center from the protein's transmembrane domain. Thus, proteolytic cleavage may act as a means of regulating mitoNEET or a mechanism by which fulllength mitoNEET abundance declines in aging cardiomyocytes.