{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T05:11:51Z","timestamp":1789189911938,"version":"build-2803163510"},"reference-count":44,"publisher":"American Society for Cell Biology (ASCB)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2016,5,15]]},"abstract":"<jats:p>Mitochondria that contain a mixture of mutant and wild-type mitochondrial (mt) DNA copies are heteroplasmic. In humans, homoplasmy is restored during early oogenesis and reprogramming of somatic cells, but the mechanism of mt-allele segregation remains unknown. In budding yeast, homoplasmy is restored by head-to-tail concatemer formation in mother cells by reactive oxygen species (ROS)\u2013induced rolling-circle replication and selective transmission of concatemers to daughter cells, but this mechanism is not obvious in higher eukaryotes. Here, using heteroplasmic m.3243A &gt; G primary fibroblast cells derived from MELAS patients treated with hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>), we show that an optimal ROS level promotes mt-allele segregation toward wild-type and mutant mtDNA homoplasmy. Enhanced ROS level reduced the amount of intact mtDNA replication templates but increased linear tandem multimers linked by head-to-tail unit-sized mtDNA (mtDNA concatemers). ROS-triggered mt-allele segregation correlated with mtDNA-concatemer production and enabled transmission of multiple identical mt-genome copies as a single unit. Our results support a mechanism by which mt-allele segregation toward mt-homoplasmy is mediated by concatemers.<\/jats:p>","DOI":"10.1091\/mbc.e15-10-0690","type":"journal-article","created":{"date-parts":[[2016,3,24]],"date-time":"2016-03-24T04:07:16Z","timestamp":1458792436000},"page":"1684-1693","source":"Crossref","is-referenced-by-count":22,"title":["Reactive oxygen species stimulate mitochondrial allele segregation toward homoplasmy in human cells"],"prefix":"10.1091","volume":"27","author":[{"given":"Feng","family":"Ling","sequence":"first","affiliation":[{"name":"Chemical Genetics Laboratory, RIKEN, Saitama 351-0198, Japan"},{"name":"Japan Agency for Medical Research and Development\u2013Core Research for Evolutional Science and Technology, Tokyo 100-0004 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Niu","sequence":"additional","affiliation":[{"name":"Chemical Genetics Laboratory, RIKEN, Saitama 351-0198, Japan"},{"name":"Japan Agency 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