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• W2126463405 abstract "Unlike most organisms, the mitochondrial DNA (mtDNA) of Chlamydomonas reinhardtii, a green alga, does not encode subunit 6 of F(0)F(1)-ATP synthase. We hypothesized that C. reinhardtii ATPase 6 is nucleus encoded and identified cDNAs and a single-copy nuclear gene specifying this subunit (CrATP6, with eight exons, four of which encode a mitochondrial targeting signal). Although the algal and human ATP6 genes are in different subcellular compartments and the encoded polypeptides are highly diverged, their secondary structures are remarkably similar. When CrATP6 was expressed in human cells, a significant amount of the precursor polypeptide was targeted to mitochondria, the mitochondrial targeting signal was cleaved within the organelle, and the mature polypeptide was assembled into human ATP synthase. In spite of the evolutionary distance between algae and mammals, C. reinhardtii ATPase 6 functioned in human cells, because deficiencies in both cell viability and ATP synthesis in transmitochondrial cell lines harboring a pathogenic mutation in the human mtDNA-encoded ATP6 gene were overcome by expression of CrATP6. The ability to express a nucleus-encoded version of a mammalian mtDNA-encoded protein may provide a way to import other highly hydrophobic proteins into mitochondria and could serve as the basis for a gene therapy approach to treat human mitochondrial diseases." @default.
• W2126463405 created "2016-06-24" @default.
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• W2126463405 date "2002-11-01" @default.
• W2126463405 modified "2023-09-30" @default.
• W2126463405 title "An Algal Nucleus-encoded Subunit of Mitochondrial ATP Synthase Rescues a Defect in the Analogous Human Mitochondrial-encoded Subunit" @default.
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• W2126463405 doi "https://doi.org/10.1091/mbc.e02-05-0306" @default.
• W2126463405 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/133596" @default.
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