title: RNA-mediated restoration of mitochondrial function in cells harboring a Kearns Sayre Syndrome mutation.
abstract: Mutations in mitochondrial DNA (mtDNA) generate multi-system disorders due to failure of ATP production. A cybrid containing a 1.9-kb mtDNA deletion from a patient with Kearns Sayre Syndrome is respiration-defective and grows glycolytically. When treated with a ribonucleoprotein (RNP) complex of polycistronic RNA 1 (pcRNA1) containing mtDNA-encoded genes and a multi-subunit carrier complex R8, full-length pcRNA1 was transported to mitochondria. Translation of the pcRNA1-encoded mRNAs was observed in mitochondria from RNP-treated cells. Respiration of the cybrid was rescued to approximately 90% of normal within hours, switching the cells to aerobic growth. These findings have implications for the development of effective mitochondrial gene therapy.
authors.affiliation: Genetic Engineering Laboratory, Indian Institute of Chemical Biology (C.S.I.R), 4 Raja S. C. Mullick Road, Calcutta 700032, India.
authors.forename: Biraj
authors.initials: B
authors.lastname: Mahato
authors.forename: Sukanta
authors.initials: S
authors.lastname: Jash
authors.forename: Samit
authors.initials: S
authors.lastname: Adhya
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D001483:Base Sequence; D002460:Cell Line; D019069:Cell Respiration; D002874:Chromosome Mapping; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism; D020869:Gene Expression Profiling; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007625:Kearns-Sayre Syndrome / Q000235:genetics* / Q000628:therapy; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000378:metabolism; D034443:RNA Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D012343:RNA, Transfer / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism / Q000494:pharmacology*; D017384:Sequence Deletion
chemical_list: D004272:DNA, Mitochondrial; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D000255:Adenosine Triphosphate; D012343:RNA, Transfer; D003576:Electron Transport Complex IV; D010100:Oxygen