title: Disruption of alternative NAD(P)H dehydrogenases leads to decreased mitochondrial ROS in Neurospora crassa.
abstract: Mitochondria are a main providers of high levels of energy, but also a major source of reactive oxygen species (ROS) during normal oxidative metabolism. The involvement of Neurospora crassa alternative NAD(P)H dehydrogenases in mitochondrial ROS production was evaluated. The growth responses of a series of respiratory mutants to several stress conditions revealed that disrupting alternative dehydrogenases leads to an increased tolerance to the redox cycler paraquat, with a mutant devoid of the external NDE1 and NDE2 enzymes being significantly more resistant. The nde1nde2 mutant mitochondria show a significant decrease in ROS generation in the presence and absence of paraquat, regardless of the respiratory substrate used, and an intrinsic increase in catalase activity. Analysis of ROS production by a complex I mutant (nuo51) indicates that, as in other organisms, paraquat-derived ROS in Neurospora mitochondria occur mainly at the level of complex I. We propose that disruption of the external NAD(P)H dehydrogenases NDE1 and NDE2 leads to a synergistic effect diminishing ROS generation by the mitochondrial respiratory chain. This, in addition to a robust increase in scavenging capacity, provides the mutant strain with an improved ability to withstand paraquat treatment.
authors.affiliation: IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150-180 Porto, Portugal. carneiro@ibmc.up.pt
authors.forename: Patrícia
authors.initials: P
authors.lastname: Carneiro
authors.forename: Margarida
authors.initials: M
authors.lastname: Duarte
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Videira
mesh_terms: D002374:Catalase / Q000378:metabolism; D015870:Gene Expression; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism; D009252:NADPH Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D009492:Neurospora crassa / Q000201:enzymology* / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D010269:Paraquat; D010641:Phenotype; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016877:Oxidants; D015800:Protozoan Proteins; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D009252:NADPH Dehydrogenase; D010269:Paraquat