Mitochondrial electron transport chain complex III activity is essential for neural differentiation of mouse P19 cell line

Abstract

Besides energy production as their main function mitochondria contribute to diverse regulatory pathways1. For instance, it has been reported that the activity of the mitochondrial electron transport chain (mETC) complexes I and III are essential for cell cycle, apoptosis and stem cell differentiation2–4. In our work, we show that mETC complex III activity is essential for neurogenic differentiation of P19 stem cells. P19 is an embryonic carcinoma mouse cell line that provides a powerful model for neurogenesis5. The efficiency of differentiation was estimated by the appearance of cells with neuron-like morphology and the detection of the neuron-specific marker protein beta-III-tubulin. The role of mETC role in P19 cell differentiation was analysed by including the mETC complex III inhibitors Antimycin A (250 nM) and Myxothiazol (10 nM), respectively, in the differentiation medium. Both Antimycin A and Myxothiazol prevented neurogenic differentiation of P19 cells. Interestingly, the inhibitors did not change the ATP/ADP ratio and hence did not affect energy production, but induced the release of reactive oxygen species (ROS) as estimated by MitoSox staining.