The importance of being acid: the role of acidification in intracellular membrane traffic

Abstract

Ever since the early work of Elie Metchnikoff at the turn of the century, it has been clear that the ability of vacuolar organelles to generate and maintain pH plays a crucial role in a variety of critical cellular functions. Using a variety of crude pH indicators such as neutral red or litmus particles, Metchnikoff observed that bacteria ingested by phagocytic cells of the immune system were transferred to acidic structures in the cytoplasm, killed and then digested. Without any understanding or knowledge of membranes, organelles or proton pumps, Metchnikoff drew accurate conclusions concerning the necessity of an acidic milieu for intracellular digestion, the role of cellular energy in maintaining the acidic pH, and the likelihood that the acidity was due to diffusible protons as opposed to the infusion of acidic substances such as DNA (which had, in fact, been offered as an explanation by some of Metchnikoff s contemporaries).