SLC25 Family Member Genetic Interactions Identify a Role for HEM25 in Yeast Electron Transport Chain Stability

摘要

The SLC25 family member SLC25A38 ( in yeast) was recently identified as a mitochondrial glycine transporter that provides substrate to initiate heme/hemoglobin synthesis. Mutations in the human SLC25A38 gene cause congenital sideroblastic anemia. The full extent to which SLC25 family members coregulate heme synthesis with other mitochondrial functions is not clear. In this study, we surveyed 29 nonessential SLC25 family members in Saccharomyces cerevisiae for their ability to support growth in the presence and absence of . Six SLC25 family members were identified that were required for growth or for heme synthesis in cells lacking function. Importantly, we determined that loss of function of the SLC25 family member , which imports FAD into mitochondria, together with loss of function of , resulted in inability to grow on media that required yeast cells to supply energy using mitochondrial respiration. We report that specific components of complexes of the electron transport chain are decreased in the absence of and function. In addition, we show that mitochondria from Δ Δ cells contain uncharacterized -containing high molecular weight aggregates. The functions of and provide a facile explanation for the decrease in heme level, and in specific electron transport chain complex components.