Overexpression of yeast karyopherin Pse1p/Kap121p stimulates the mitochondrial import of hydrophobic proteins in vivo

During evolution, cellular processes leading to the transfer of genetic inf ormation failed to send all the mitochondrial genes into the nuclear genome . Two mitochondrial genes are still exclusively located in the mitochondria l genome of all living organisms. They code for two highly hydrophobic prot eins: the apocytochrome b and the subunit I of cytochrome oxidase. Assuming that the translocation machinery could not efficiently transport long hydr ophobic fragments, we searched for multicopy suppressors of this physical b lockage. We demonstrated that overexpression of Pse1p/Kap121p or Kap123p, w hich belong to the superfamily of karyopherin beta proteins, facilitates th e translocation of chimeric proteins containing several stretches of apocyt ochrome b fused to a reporter mitochondrial gene. The effect of PSE1/KAP121 overexpression tin which PSE1 is protein secretion enhancer 1) on mitochon drial import of the chimera is correlated with an enrichment of the corresp onding transcript in cytoplasmic ribosomes associated with mitochondria. PS E1/KAP121 overexpression also improves the import of the hydrophobic protei n Atm1p, an ABC transporter of the mitochondrial inner membrane. These resu lts suggest that in vivo PSE1/KAP121 overexpression facilitates, either dir ectly or indirectly, the co-translational import of hydrophobic proteins in to mitochondria.