Disruption of alternative NAD(P)H dehydrogenases leads to decreased mitochondrial ROS in Neurospora crassa

作者：Carneiro Patricia^*; Duarte Margarida; Videira Arnaldo

来源：Free Radical Biology and Medicine, 2012, 52(2): 402-409.

DOI：10.1016/j.freeradbiomed.2011.10.492

• Mitochondria
• NAD(P)H dehydrogenase
• Respiratory mutant
• Paraquat
• Reactive oxygen species
• Neurospora crassa
• Free radicals

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.

• 出版日期2012-1-15