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Abstract
Mitochondrial alternative NADH dehydrogenase (aNDH) was found to extend lifespan when expressed in the fruit fly. We have found that fruit flies expressing aNDH from Ciona intestinalis (NDX) had 17–71% lifespan prolongation on media with different protein-tocarbohydrate ratios except NDX-expressing males that had 19% shorter lifespan than controls on a high protein diet. NDX-expressing flies were more resistant to organic xenobiotics, 2,4-dichlorophenoxyacetic acid and alloxan, and inorganic toxicant potassium iodate, and partially to sodium molybdate treatments. On the other hand, NDX-expressing flies were more sensitive to catechol and sodium chromate. Enzymatic analysis showed that NDX-expressing males had higher glucose 6-phosphate dehydrogenase activity, whilst both sexes showed increased glutathione S-transferase activity.
Highlights
Many organisms, but not insects, contain unconventional, ‘alternative’ enzymes in their mitochondrial respiratory chains (RC) (Matus-Ortega et al 2011; McDonald and Gospodaryov 2019)
In the majority of above-mentioned studies, lifespan extension was achieved by using Ndi1, an alternative NADH dehydrogenase (aNDH) derived from the budding yeast Saccharomyces cerevisiae
In 2014, we first revealed that the enzyme of animal origin, from tunicate Ciona intestinalis, was able to prolong lifespan of the fruit fly Drosophila melanogaster being heterologously expressed in its body (Gospodaryov et al 2014)
Summary
But not insects, contain unconventional, ‘alternative’ enzymes in their mitochondrial respiratory chains (RC) (Matus-Ortega et al 2011; McDonald and Gospodaryov 2019). These enzymes catalyse reactions similar to those catalysed by the Present Address: B. In the majority of above-mentioned studies, lifespan extension was achieved by using Ndi, an aNDH derived from the budding yeast Saccharomyces cerevisiae. In 2014, we first revealed that the enzyme of animal origin, from tunicate Ciona intestinalis, was able to prolong lifespan of the fruit fly Drosophila melanogaster being heterologously expressed in its body (Gospodaryov et al 2014). Whatever the source of the enzyme, the mechanism of the lifespan extension by means of aNDH remained obscure. Alternative NDH allows a partial bypass of mitochondrial RC complex I, one of the main generators of reactive oxygen species (ROS) which damage essential cellular components, including mitochondrial DNA
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