ER-mitochondria contacts couple mtDNA synthesis with Mitochondrial division in human cells

Samantha C. Lewis, Lauren F. Uchiyama, Jodi Nunnari

Research output: Contribution to journalArticle

186 Scopus citations

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.

Original languageEnglish (US)
Article numberaaf5549
JournalScience
Volume353
Issue number6296
DOIs
StatePublished - Jul 15 2016

ASJC Scopus subject areas

  • Medicine(all)
  • General

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