THE YEAST GENE, MDM20, IS NECESSARY FOR MITOCHONDRIAL INHERITANCE ANDORGANIZATION OF THE ACTIN CYTOSKELETON

In Saccharomyces cerevisiae, the growing bud inherits a portion of the mitochondrial network from the mother cell soon after it emerges. Alt hough this polarized transport of mitochondria is thought to require f unctions of the cytoskeleton, there are conflicting reports concerning the nature of the cytoskeletal element involved. Here we report the i solation of a yeast mutant, mdm20, in which both mitochondrial inherit ance and actin cables (bundles of actin filaments) are disrupted. The MDM20 gene encodes a 93-kD polypeptide with no homology to other chara cterized proteins. Extra copies of TPM1, a gene encoding the actin fil ament-binding protein tropomyosin, suppress mitochondrial inheritance defects and partially restore actin cables in mdm20 Delta cells. Synth etic lethality is also observed between mdm20 and tpm1 mutant strains. Overexpression of a second yeast tropomyosin, Tpm2p, rescues mutant p henotypes in the mdm20 strain to a lesser extent. Together, these resu lts provide compelling evidence that mitochondrial inheritance in yeas t is an actin-mediated process. MDM20 and TPM1 also exhibit the same p attern of genetic interactions; mutations in MDM20 are synthetically l ethal with mutations in BEM2 and MYO2 but not SAC6. Although MDM20 and TPM1 are both required for the formation and/or stabilization of acti n cables, mutations in these genes disrupt mitochondrial inheritance a nd nuclear segregation to different extents. Thus, Mdm20p and Tpm1p ma y act in vivo to establish molecular and functional heterogeneity of t he actin cytoskeleton.