Loss of Dja2 accompanies pH deviation in lysosomes and lysosome‐related organelles.

The Dja2 knockout (Dja2−/−) mice had respiratory distress, and >60% died within 2 days after birth. The surviving adult Dja2−/− mice were infertile and the lungs of Dja2−/− mice showed several abnormalities, including the processing defect of prosurfactant protein C in the alveolar epithelial type II cells and the accumulation of glycolipids in enlarged alveolar macrophages. The luminal pH of acidic organelles in Dja2−/− cells was shifted to pH 5.37–5.45. This deviated pH was immediately restored to control levels (pH 4.56–4.65) by the addition of a diuretic, ethyl isopropyl amiloride (EIPA). Although the role of DJA2 in maintaining the pH homeostasis of lysosome‐related organelles is currently obscure, this rapid and remarkable pH resilience is best explained by an EIPA‐sensitive proton efflux machinery that is disorganized and overactivated due to the loss of Dja2. [ABSTRACT FROM AUTHOR]