A Novel Implication of the Physiological Importance of Local Protons at the Membrane Surface of Organellar Vesicles in Eukaryote Cells: Organellar Type Na + /H + Exchanger Nhx1p from Saccharomyces cerevisiae Plays an Important Role in the Formation of Multivesicular Bodies

Intracellular pH homeostasis is the essential element for living cells. Optimal pH has to be provided for proteins to function properly within the cells. pH is kept at around 7.3 in most cells from bacterial to mammalian. In contrast, for various endosomes in the cytoplasm their own weak acidic pH is maintained. For the homeostatic pH regulation in the compartments like cytoplasm and endosomal lumen are performed by H transporting membrane integral proteins. One of these is the Na/H exchanger (NHE or Nha). Here the roles of Na/H exchangers in the cells are summarized based on our recent findings. One of the most important findings is that the acidic pH regulated by NHE in the yeast endosomes contributes to recruitment of various factors required for membrane protein trafficking on the membrane surface of the endosomes. This acidic pH leads to multivesicular body (MVB) formation. These observations raise a new important role for NHE, not only in the pH regulation of the endosome lumen but also for pH regulation on the cytoplasmic surface of the endosomes. Based on this new physiological role of organellar NHE from yeast (Nhx1) we propose a new conceptual idea of the importance of local protons regulated by the NHEs in cell physiology.