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

作者：Lewis, Samantha C.; Uchiyama, Lauren F.; Nunnari, Jodi^*

来源：Science, 2016, 353(6296): aaf5549.

DOI：10.1126/science.aaf5549

• DNA-POLYMERASE-GAMMA
• TUBULAR ENDOPLASMIC-RETICULUM
• HEREDITARY SPASTIC PARAPLEGIA
• REPLICATION
• MEMBRANE
• NUCLEOIDS
• TFAM
• TRANSCRIPTION
• MAINTENANCE
• DYNAMICS

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.

• 出版日期2016-7-15