High expression of the aspartate–glutamate carrier Aralar1 favors lactate consumption in CHO cell culture

Process performance of mammalian cell cultures can be strongly impacted by high lactate accumulation, which can be a clone or media-dependent characteristic. In this study, the expression of specific genes was measured in several Chinese hamster ovary cell lines under culture conditions leading to different lactate profiles. A reduced expression of two genes was observed under conditions of high lactate accumulation: AGC1/Aralar1, a member of the malate–aspartate shuttle (MAS) and Timm8a1. Overexpression of either of these two genes in the lactate-producing cell line diminished lactate accumulation. This was achieved by promoting a metabolic switch to lactate consumption after day 6, while maintaining a glycolytic rate similar to the parental cells. On the other hand, the biochemical inhibition of MAS activity increased lactate accumulation. All together, these results indicate MAS as a key factor to promote a shift to lactate consumption in cultivated Chinese hamster ovary cells.