RNA-mediated restoration of mitochondrial function in cells harboring a Kearns Sayre Syndrome mutation

Mitochondrion. 2011 Jul;11(4):564-74. doi: 10.1016/j.mito.2011.03.006. Epub 2011 Mar 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Base Sequence
  • Cell Line
  • Cell Respiration
  • Chromosome Mapping
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism*
  • Electron Transport Complex IV / metabolism
  • Gene Expression Profiling
  • Gene Transfer Techniques*
  • Genetic Therapy
  • Humans
  • Kearns-Sayre Syndrome / genetics*
  • Kearns-Sayre Syndrome / therapy
  • Membrane Potential, Mitochondrial
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Mitochondria / physiology*
  • Oxidative Phosphorylation
  • Oxygen / metabolism
  • RNA Transport
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Messenger / pharmacology
  • RNA, Transfer / metabolism
  • Ribonucleoproteins / metabolism
  • Ribonucleoproteins / pharmacology*
  • Sequence Deletion

Substances

  • DNA, Mitochondrial
  • RNA, Messenger
  • Ribonucleoproteins
  • Adenosine Triphosphate
  • RNA, Transfer
  • Electron Transport Complex IV
  • Oxygen