title: Parkin modulates heteroplasmy of truncated mtDNA in Caenorhabditis elegans.
abstract: Parkin, which is mutated in most recessive Parkinsonism, is a key player in the selective removal of damaged mitochondria via mitophagy. Damaged mitochondria may carry mitochondrial DNA (mtDNA) mutations, thus creating a mixed mtDNA population within cells (heteroplasmy). It was previously shown that Parkin over-expression reduced the level of heteroplasmic mutations that alter mitochondrial membrane potential in human cytoplasmic hybrids. However, it remained unclear whether Parkin serves a similar role at the entire living organism, and whether this role is evolutionarily conserved. Here, we show that mutation in the Caenorhabditis elegans orthologue of Parkin (pdr-1) modulates the level of a large heteroplasmic mtDNA truncation. Massive parallel sequencing revealed that the mtDNAs of C. elegans wild type and pdr-1(gk448) mutant strains were virtually deprived of heteroplasmy, thus reflecting strong negative selection against dysfunctional mitochondria. Therefore, our findings show that the role of Parkin in the modulation of heteroplasmy is conserved between human and worm and raise the interesting possibility that mitophagy modulates the striking lack of heteroplasmy in C. elegans.
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel; The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.
authors.forename: Itay
authors.initials: I
authors.lastname: Valenci
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel; The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.
authors.forename: Lital
authors.initials: L
authors.lastname: Yonai
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Bar-Yaacov
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Mishmar
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel; The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel. Electronic address: anatbz@bgu.ac.il.
authors.forename: Anat
authors.initials: A
authors.lastname: Ben-Zvi
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D009154:Mutation; D011110:Polymorphism, Genetic; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein
keywords: Caenorhabditis elegans; Heteroplasmy; Mitochondria; PINK1; Parkin; mtDNA