Genetic correction of mitochondrial diseases: using the natural migration of mitochondrial genes to the nucleus in chlorophyte algae as a model system

Annals of the New York Academy of Sciences
Diego González-HalphenMichael P King

Abstract

Mitochondrial diseases display great diversity in clinical symptoms and biochemical characteristics. Although mtDNA mutations have been identified in many patients, there are currently no effective treatments. A number of human diseases result from mutations in mtDNA-encoded proteins, a group of proteins that are hydrophobic and have multiple membrane-spanning regions. One method that has great potential for overcoming the pathogenic consequences of these mutations is to place a wild-type copy of the affected gene in the nucleus, and target the expressed protein to the mitochondrion to function in place of the defective protein. Several respiratory chain subunit genes, which are typically mtDNA encoded, are nucleus encoded in the chlorophyte algae Chlamydomonas reinhardtii and Polytomella sp. Analysis of these genes has revealed adaptations that facilitated their expression from the nucleus. The nucleus-encoded proteins exhibited diminished physical constraints for import as compared to their mtDNA-encoded homologues. The hydrophobicity of the nucleus-encoded proteins is diminished in those regions that are not involved in subunit-subunit interactions or that contain amino acids critical for enzymatic reactions of the proteins....Continue Reading

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Citations

May 22, 2008·Genetics·Francisco Figueroa-MartínezDiego González-Halphen
Feb 25, 2014·Mitochondrion·Miriam Vázquez-AcevedoDiego González-Halphen
Jun 23, 2012·Molecular Phylogenetics and Evolution·Elizabeth Rodríguez-SalinasDiego González-Halphen
Mar 20, 2012·Biochimica Et Biophysica Acta·Alejandra Jiménez-SuárezDiego González-Halphen
Feb 14, 2018·Molecular Biology of the Cell·Diana Rubalcava-GraciaDiego González-Halphen
Jul 19, 2019·Molecular Biology of the Cell·Diana Rubalcava-GraciaDiego González-Halphen

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