title: Rapamycin reduces oxidative stress in frataxin-deficient yeast cells.
abstract: Friedreich ataxia (FRDA) is a common form of ataxia caused by decreased expression of the mitochondrial protein frataxin. Oxidative damage of mitochondria is thought to play a key role in the pathogenesis of the disease. Therefore, a possible therapeutic strategy should be directed to an antioxidant protection against mitochondrial damage. Indeed, treatment of FRDA patients with the antioxidant idebenone has been shown to improve neurological functions. The yeast frataxin knock-out model of the disease shows mitochondrial iron accumulation, iron-sulfur cluster defects and high sensitivity to oxidative stress. By flow cytometry analysis we studied reactive oxygen species (ROS) production of yeast frataxin mutant cells treated with two antioxidants, N-acetyl-L-cysteine and a mitochondrially-targeted analog of vitamin E, confirming that mitochondria are the main site of ROS production in this model. Furthermore we found a significant reduction of ROS production and a decrease in the mitochondrial mass in mutant cells treated with rapamycin, an inhibitor of TOR kinases, most likely due to autophagy of damaged mitochondria.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Department of Pharmaco-Biology, University of Bari, Via E. Orabona 4, 70125 Bari, Italy.
authors.forename: Carlo M T
authors.initials: CM
authors.lastname: Marobbio
authors.forename: Isabella
authors.initials: I
authors.lastname: Pisano
authors.forename: Vito
authors.initials: V
authors.lastname: Porcelli
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Lasorsa
authors.forename: Luigi
authors.initials: L
authors.lastname: Palmieri
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D005434:Flow Cytometry; D017353:Gene Deletion; D033862:Iron-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000032:analysis; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology*; D013312:Stress, Physiological; D000096923:Frataxin
chemical_list: D000975:Antioxidants; D033862:Iron-Binding Proteins; D017382:Reactive Oxygen Species; D020123:Sirolimus; D000096923:Frataxin