Mitochondrial energy metabolism regulates the nutrient import activity and endocytosis of APC transporters.

Nutrient import by APC-type transporters is predicted to have a high energy demand because it depends on the plasma membrane proton gradient established by the ATP-driven proton pump Pma1. We show that Pma1 is indeed a major energy consumer and its activity is tightly linked to the cellular ATP levels. The low Pma1 activity caused by acute loss of respiration resulted in a dramatic drop in cytoplasmic pH, which triggered the downregulation of the major proton importers, the APC transporters. This regulatory system is likely the reason for the observed rapid endocytosis of APC transporters during many environmental stresses. Furthermore, we show the importance of respiration in providing ATP to maintain a strong proton gradient for efficient nutrient uptake.