Yeast homologs of MCUR1 regulate mitochondrial proline metabolism

MCUR1 is an evolutionarily conserved mitochondrial protein that has been shown to act as a scaffold factor for the assembly of the mammalian mitochondrial calcium uniporter (MCU). Surprisingly, many fungi that do not have MCU contain MCUR1 homologs, suggesting these proteins possess alternate functions. Herein we characterized two Saccharomyces cerevisiae homologs of MCUR1- Put6 and Put7 as regulators of mitochondrial proline metabolism. Put6 and Put7 are tethered to the inner mitochondrial membrane in a large hetero-oligomeric complex. The abundance and assembly of this complex are regulated by proline and the loss of this complex results in unregulated proline uptake in the mitochondria, leading to redox imbalance in the cell. Yeast cells lacking either Put6 or Put7 exhibit a pronounced defect in proline utilization, which can be corrected by the heterologous expression of human MCUR1. Our work uncovers an unexpected role of evolutionarily conserved MCUR1 homologs in mitochondrial proline metabolism.