Abstract: We here identify Med5 (Nut1) as a component of the Mediator tail region. Med5 is positioned peripherally to Med16 (Sin4), together with the three members of the putative Gal11 module: Med15 (Gal11), Med2, and Med3 (Pgd1). The biochemical analysis receives support from genetic interactions between med5D and med15D deletions. The med5D and med16D deletion strains share many phenotypes, including effects on mitochondrial function with enhanced growth on non-fermentable carbon sources, increased citrate synthase activity and increased oxygen consumption. Deletion of the MED5 gene leads to increased transcription of nuclear genes encoding components of the oxidative phosphorylation machinery, whereas mitochondrial genes encoding components of the same machinery are down regulated. We discuss a possible role for Med5 in coordinating nuclear and mitochondrial gene transcription.