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  • Aspergillus nigerA niger is another

    2021-02-24

    Aspergillus nigerA. niger is another filamentous fungus, in which alternative dehydrogenases have been described. Filamentous fungi are a very important group of microorganisms that are used in industry (O’Donnell et al. 2011). Biotechnological production processes using these organisms are often highly aerobic, thus implying that the fungal cells are subjected to oxidative stress. The presence and activity of type II dehydrogenases in Aspergilli have garnered much interest due to their possible antioxidative role in mitochondria. Basing on homology to other fungi and the availability of Aspergillus species genomes, putative nde and ndi genes encoding alternative external and internal NADH dehydrogenases, respectively, have been found (Li et al. 2011). The analysis of the genomes reveals high levels of conservation and genome synteny across the Aspergillus species, indicating that these dehydrogenases play a fundamental role in fungal growth in the natural environment in response to oxidative stress. In addition, the dehydrogenases provide useful tools in industrial bioprocesses. In A. niger, the activity of alternative NADH dehydrogenases increases significantly under oxidative stress conditions, while no changes in ROS concentration have been found (O’Donnell et al. 2011). It has been suggested that under oxidative stress conditions, a decrease in ATP production and a diminished capability for highly energetic processes could be a consequence of the enhanced activity of alternative NADH dehydrogenases. Interestingly, these effects lead to a decrease in cellular viability and subsequently cause earlier senescence and culture death. Additional studies have revealed that inhibition of the alternative NADH dehydrogenases by the most effective inhibitor 7-iodoacridone 4-carboxylic pilocarpine hcl synthesis (IACA) enhances metabolic activity and almost doubles amount of ATP produced in A. niger cells (Voulgaris et al. 2012). Thus, these reports show that the inhibition of the alternative NADH dehydrogenases has noticeable effects on the productivity of a bioprocess under moderate oxygenation conditions. It has been suggested that the application of an alternative NADH dehydrogenase deficient mutant, together with the appropriate fermentation conditions, could be a route to significantly increase the productivity of an industrial fungal bioprocess by increasing the growth rate and consequently reducing the fermentation times while at the same time increasing the energetic efficiency (Voulgaris et al. 2012).
    Type II NAD(P)H Dehydrogenases in Protists TrypanosomaParasitic protozoans have been extensively investigated due to the search for new effective drugs for the dangerous diseases they cause. Because mammalian mitochondria do not possess alternative dehydrogenase in the respiratory chain, these proteins have become a specific potential target for disease treatment. The African trypanosome T. brucei, the causal agent of sleeping sickness in humans and nagana in cattle, has a dual life cycle in the bloodstream of the mammalian host and the insect vector (Bienen et al., 1991, Hajduk et al., 1992). In the mammalian bloodstream, the trypanosomes exist as dividing long slender forms that lack well-developed mitochondria, cytochromes, and cyanide-sensitive electron transport. In these developmental forms, energy requirements are provided completely by glycolysis using glucose from the blood of the mammalian host (Opperdoes 1987). However, the procyclic forms, present in the midgut of the insect host, possess a single, large mitochondrion containing respiratory chain complexes generally similar to those present in eukaryotes (Hajduk et al. 1992). In 2003, an alternative NADH dehydrogenase from the T. brucei procyclic form (NDH2) was isolated and characterized (Fang and Beattie 2003b). The enzyme is rotenone-insensitive and contains noncovalently bound FMN as a cofactor, instead of the FAD usually present in eukaryotic type II dehydrogenases. FMN appears to serve as one electron donor to UQ or oxygen in contrast to the two-electron reduction conducted by FAD. This feature fosters ROS production, since superoxide is generated by a one-electron reduction of molecular oxygen. A previous study confirmed that the rotenone-insensitive NADH dehydrogenase is a potential source of superoxide production in procyclic trypanosome mitochondria (Fang and Beattie 2002b). The T. brucei alternative NADH dehydrogenase is a dimer of 65kDa, which separates into two 33kDa subunits, and is located on the inner mitochondrial membrane facing the matrix (Fang and Beattie 2003b). Because of a low Complex I activity, one of possible functions for NDH2 in T. brucei mitochondria is to complement Complex I, mediating electron transfer from internal NADH to the respiratory chain. Subsequent studies on the requirement for the core subunits of Complex I in the T. brucei respiratory chain lead to conclusion that Complex I activity can be fully replaced by NDH2 (Verner et al. 2013). In addition, the enzyme is capable of utilizing deamino NADH and NADPH as substrates in vitro (Fang and Beattie 2003b). Interestingly, the mitochondria of the procyclic T. brucei depleted of Complex I subunits exhibit an increased sensitivity of the NADH oxidation to diphenyloiodonium chloride (IDP) and a lower sensitivity to rotenone, a specific inhibitor of Complex I (Verner et al. 2011). However, the depletion of NDH2 affects both cell growth and the mitochondrial membrane potential, although the remaining activities of the respiratory complexes are unaltered with an exception of the increased activity of glycerol-3-phosphate dehydrogenase (Verner et al. 2013). These results support the hypothesis that in the procyclic T. brucei mitochondrion, NDH2 might be preferentially used to regenerate NAD+ and maintain the mitochondrial membrane potential compared to Complex I.