Activation of the p66Shc pathway in mitochondria-related pathologies

Abstract

have a channel activity [6], mitochondria from ΔPOR1 strain imported significant amount of tRK1 in presence of cytb2-DHFR. Experiments with vesicles prepared from outer membrane of wild type and ΔPOR1,2 mitochondria confirmed the essential role of Por2 protein in tRK1 import. Finally, first time isolated homogenous Por2 was reconstituted into small unilamellar vesicles and planar phospholipid bilayer membranes. With proteoliposomes it was shown that Por2 provides transport of carbohydrates and nucleotides across the membrane with the same kinetic as for Por1 and on bilayer system cation selective channels were registered with conductivity about 2 nS and closure with voltage above 30 mV in pH dependent manner. Physiological role of Por2 and downregulation mechanism of its channel activity in mitochondrial outer membrane are discussed. An understanding of the fine mechanisms of tRNA import from cytosol could help us to improve delivery of “therapeutic” RNA molecules into mitochondria to cure at themolecular level the negative effects of mutations of tRNA genes coded by the mitochondrial DNA causes large number of human diseases, such as Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) or Myoclonic Epilepsy with Ragged Red Fibers (MERRF) [7].