WM-2474 Aspergillus nigerA niger is another filamentous fung

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 WM-2474 (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 ApicomplexansApicomplexans are unicellular and spore-forming obligate intracellular parasites that occupy diverse host niches (Mogi and Kita 2010). They have remodeled mitochondrial carbon and energy metabolism through reductive evolution. The development of novel drugs is now a very serious challenge in the face of the increasing problem of the multidrug resistance of Plasmodium that causes malaria in humans. The function of the Plasmodium mitochondria is unclear because it is widely accepted that the majority of the energetic demand of the parasite is provided by glycolysis. In addition, it has been suggested for a long time that the Plasmodium mitochondria cannot conduct oxidative phosphorylation, because they lack the membrane anchor subunits for ATP synthase. However, it has been shown that the mitochondria can generate a large transmembrane potential (Biagini et al. 2006). Ten subunits of Plasmodium FoF1-ATP synthase, including membrane anchor subunits a and b, were finally identified, although they are highly divergent from their eukaryotic and bacterial counterparts (Kawahara et al. 2009). Thus, the Plasmodium mitochondria appear to be capable of oxidative phosphorylation. However, it is more likely that the mitochondria of these malaria parasites are engaged in cellular functions other than ATP synthesis, such as calcium homeostasis maintenance or pyrimidine synthesis (Stocks et al. 2014).