Inhibition of mitochondrial protein synthesis promotes autonomous regulation of mtDNA expression and generation of a new mitochondrial RNA species.
Mammalian mitochondria are known to proliferate in response to several stimuli. Proliferation requires an increase in expression of genes encoding proteins involved in mitochondrial biogenesis, as well as in the replication and expression of mitochondrial DNA (mtDNA). In contrast, we report that inhibiting mitochondrial protein synthesis causes a modulation in mtDNA gene expression without the concomitant increase in proliferative markers. Further, inhibition results in the production of a previously unidentified light-strand mitochondrial RNA that spans the entire displacement loop, the function of which is currently unknown.
Selwood
S P
SP
Neuroscience Research Laboratories, Department of Psychiatry, Stanford University School of Medicine, Stanford, CA 94305-5485, USA.
McGregor
A
A
Lightowlers
R N
RN
Chrzanowska-Lightowlers
Z M
ZM
D001483:Base Sequence; D004261:DNA Replication / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D051264:Nuclear Respiratory Factors; D014176:Protein Biosynthesis / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077278:RNA, Mitochondrial; D013839:Thiamphenicol / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D051264:Nuclear Respiratory Factors; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D000077278:RNA, Mitochondrial; D015534:Trans-Activators; D012313:RNA; D013839:Thiamphenicol