Mitochondrial dysfunction typically causes a shift towards glycolysis, as is seen in many cancer cells. However, the mechanisms remain poorly understood. The effects of mitochondrial dysfunction also cause a rise in glutamine catabolism, but how this links to increased glycolysis has not been fully explained. Recently, a novel isogenic cell line with reduced levels of m.8993T>G mutation heteroplasmy, named mTUNE (mT), was created that allowed greater clarity of central carbon metabolism to be investigated.

Using mTUNE (mT) cells, it has been shown that mitochondrial respiration could be rescued by the expression of NDI-1 originally from yeast. NDI-1 replaced the NADH oxidoreductase activity where respiratory chain complex I function is compromised. NDI-1 was visualised in western blots and injected into cells to quantify oxygen consumption rate measurement following a challenge with a known disruptor of the electron transport chain. The expression of NDI-1 increased the ratio of NAD+/NADH and diminished the reductive metabolism of glutamine. NDI-1 and the anti-NDI-1 antibody were vital in proving that dysregulated mitochondrial NADH cycling induces reductive carboxylation of glutamine by an impaired cytosolic NAD+/NADH ratio.  Further work with NDI-1 and the anti-NDI-1 antibody could provide additional insights into the nature of the relationship and the link between glycolysis and mitochondrial dysfunction.