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

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 similar to 90% of normal within hours, switching the cells to aerobic growth. These findings have implications for the development of effective mitochondrial gene therapy. (C) 2011 Elsevier B.V. and Mitochondria Research Society. All rights reserved.