The amino-terminal region of an imported mitochondrial precursor polypeptide can direct cytoplasmic dihydrofolate reductase into the mitochondrial matrix.
Subunit IV of yeast cytochrome c oxidase is encoded by a nuclear gene, synthesized in the cytosol as a precursor with a transient amino-terminal extension of 25 amino acids, and imported into the mitochondria. By gene fusion, we have attached the amino-terminal 53 amino acids of the subunit IV precursor to the amino terminus of the mouse cytosolic enzyme dihydrofolate reductase. When the resulting fusion protein was synthesized in a transcription-translation system and then incubated with energized yeast mitochondria, it was imported into the mitochondrial matrix space and processed to a shorter form by the chelator-sensitive matrix protease. No evidence was obtained that the fusion protein became stuck across one of the two mitochondrial membranes. Thus, a non-mitochondrial protein can be transported into the mitochondrial matrix if it is fitted with a mitochondrial targeting sequence.
D000595:Amino Acid Sequence; D001693:Biological Transport, Active; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism*
D011498:Protein Precursors; D013762:Tetrahydrofolate Dehydrogenase; D003576:Electron Transport Complex IV