The Housekeeping Transporter SLC25A44 Bridges between the Secondary Metabolism and Mitochondrial Electron Transfer Chains

The solute carrier family 25 (SLC25) participates in the transport of metabolites and cofactors across the membranes of mitochondria, plastids, peroxisomes, and endoplasmic reticulum. By calling for genomic blocks involved in adjacent metabolic reactions, this report introduces gene clusters of the Slc25 subfamily 44, stilbene and chalcone synthases, and subunits of the mitochondrial electron transfer complexes. The Slc25A44 gene was found ubiquitously expressed and transcriptionally co-regulated with energy metabolism genes in human, mouse, and Arabidopsis thaliana. The Slc25A44s also had no homozygous missense mutation and were highly conserved at intra-species level with the majority of polymorphism present in the non-coding regions. When expressed in oocytes, AdSlc25A44 from Arachis duranensis showed transport activity for the common precursors of flavonoids, stilbenoids, and ubiquinone. Accordingly, AdSLC25A44 and its human orthologue HsSLC25A44 elevated the production of para-coumaric, 4-aminobenzoic, and 4-hydroxybenzoic acids in Saccharomyces cerevisiae strains designed to produce para-coumaric acid via different pathways. Moreover, the engineered SLC25 subfamily specific signature, i.e., AdSLC25A44LWW206IQF, had a stronger effect on para-coumaric acid secretion than the native variant. Importantly, the aerobic growth-rate of S. cerevisiae was significantly higher when expressing the AdSLC25A44, HsSLC25A44, or AdSLC25A44LWW206IQF. These results suggest that SLC25A44 is an essential mitochondrion-ER-nucleus zone transporter associated with metabolism of secondary metabolites and energy.