ArticleMolecular biology of the cell2002
An algal nucleus-encoded subunit of mitochondrial ATP synthase rescues a defect in the analogous human mitochondrial-encoded subunit.
Article in Molecular biology of the cell, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 59 citations in OpenAlex.
- Gene Therapy Tools for Diseases Caused by Mutations of the Mitochondrial Genome.International journal of molecular sciences · 2026Review
- Mitochondrial genomes revisited: why do different lineages retain different genes?BMC biology · 2024Review
- The Mitochondrial Genome in Aging and Disease and the Future of Mitochondrial Therapeutics.Biomedicines · 2022Review
- ATP synthase hexamer assemblies shape cristae of Toxoplasma mitochondria.Nature communications · 2021Article
- ER-resident sensor PERK is essential for mitochondrial thermogenesis in brown adipose tissue.Life science alliance · 2020Article
- Codon optimization is an essential parameter for the efficient allotopic expression of mtDNA genes.Redox biology · 2020Article
- Mitochondrial supercomplex assembly promotes breast and endometrial tumorigenesis by metabolic alterations and enhanced hypoxia tolerance.Nature communications · 2019Article
- Key within-membrane residues and precursor dosage impact the allotopic expression of yeast subunit II of cytochromeMolecular biology of the cell · 2019Article
- Mitochondrial versus nuclear gene expression and membrane protein assembly: the case of subunit 2 of yeast cytochromeMolecular biology of the cell · 2018Article
- Mitochondrial ATP synthase: architecture, function and pathology.Journal of inherited metabolic disease · 2012Review
- Leber's Hereditary Optic Neuropathy-Gene Therapy: From Benchtop to Bedside.Journal of ophthalmology · 2011Article
- Allotopic expression of mitochondrial-encoded genes in mammals: achieved goal, undemonstrated mechanism or impossible task?Nucleic acids research · 2011Article
- The approaches for manipulating mitochondrial proteome.Environmental and molecular mutagenesis · 2010Review
- Biochemical analysis of respiratory function in cybrid cell lines harbouring mitochondrial DNA mutations.The Biochemical journal · 2004Article
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5 authors at 2 institutions in 1 country.
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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.
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