Mmf1p, a novel yeast mitochondrial protein conserved throughout evolution and involved in maintenance of the mitochondrial genome

A novel protein family (p14.5, or YERO57c/YJGFc) highly conserved throughou t evolution has recently been identified. The biological role of these prot eins is not yet well characterized. Two members of the p14.5 family are pre sent in the yeast Saccharomyces cerevisiae. In this study, we have characte rized some of the biological functions of the two yeast proteins. Mmf1p is a mitochondrial matrix factor, and homologous Mmf1p factor (Hmf1p) copurifi es with the soluble cytoplasmic fraction. Delta mmf1 cells lose mitochondri al DNA (mtDNA) and have a decreased growth rate, while Delta hmf1 cells do not display any visible phenotype. Furthermore, we demonstrate by genetic a nalysis that Mmf1p does not play a direct role in replication and segregati on of the mtDNA, rho(+) Delta mmf1 haploid cells can be obtained when tetra ds are directly dissected on medium containing a nonfermentable carbon sour ce. Our data also indicate that Mmf1p and Hmf1p have similar biological fun ctions in different subcellular compartments. Hmf1p, when fused with the Mm f1p leader peptide, is transported into mitochondria and is able to functio nally replace Mmf1p. Moreover, we show that homologous mammalian proteins a re functionally related to Mmf1p. Human p14.5 localizes in yeast mitochondr ia and rescues the Delta mmf1-associated phenotypes. In addition, fractiona tion of rat liver mitochondria showed that rat p14.5, like Mmf1p, is a solu ble protein of the matrix. Our study identifies a biological function for M mf1p and furthermore indicates that this function is conserved between memb ers of the p14.5 family.