title: ER-mitochondria contacts couple mtDNA synthesis with mitochondrial division in human cells.
abstract: Mitochondrial DNA (mtDNA) encodes RNAs and proteins critical for cell function. In human cells, hundreds to thousands of mtDNA copies are replicated asynchronously, packaged into protein-DNA nucleoids, and distributed within a dynamic mitochondrial network. The mechanisms that govern how nucleoids are chosen for replication and distribution are not understood. Mitochondrial distribution depends on division, which occurs at endoplasmic reticulum (ER)-mitochondria contact sites. These sites were spatially linked to a subset of nucleoids selectively marked by mtDNA polymerase and engaged in mtDNA synthesis--events that occurred upstream of mitochondrial constriction and division machine assembly. Our data suggest that ER tubules proximal to nucleoids are necessary but not sufficient for mtDNA synthesis. Thus, ER-mitochondria contacts coordinate licensing of mtDNA synthesis with division to distribute newly replicated nucleoids to daughter mitochondria.
authors.affiliation: Department of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA.
authors.forename: Samantha C
authors.initials: SC
authors.lastname: Lewis
authors.affiliation: Department of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA.
authors.forename: Lauren F
authors.initials: LF
authors.lastname: Uchiyama
authors.affiliation: Department of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA. jmnunnari@ucdavis.edu.
authors.forename: Jodi
authors.initials: J
authors.lastname: Nunnari
mesh_terms: D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000096:biosynthesis*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000502:physiology* / Q000648:ultrastructure; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D063154:Mitochondrial Dynamics; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D004259:DNA-Directed DNA Polymerase; C544932:POLG2 protein, human