ABSTRACT

Intracellular pH (pHi) is one of t he f undamental modulators of cell f unction (Srivastava et a l. 2007). Owing to the high reactivity of H+ ions with proteins and other biomolecules, pHi plays a major role in processes as varied as cell metabolism and growth (Wang et a l. 1997, Putney and Barber 2003), ionic current ow t hrough memb rane c hannels a nd c ellular e xcitability, s olute movemen t on memb rane transporter proteins (and therefore general ion homeostasis) (Fliegel 2005, Hunte et al. 2005), and muscle cellular contractility (Wakabayashi et al. 2006). Alterations of pHi strongly a ect cell viability. For instance, mitochondria are characterized by mildly alkaline pH and deviations from this pattern may lead to cell apoptosis (Abad et al. 2004). e aberrations of the normal organellar pH homeostasis can lead to a n impairment of posttranslational modi cations and processing of secreted proteins (Carnell and Moore 1994), to a mislocalization of the biosynthetic cargo (Chanat and Huttner 1991), and to severe defects in the functionality of organelles (Puri et al. 2002). Abnormalities noted in many human tumors

(i.e., breast cancer and colorectal cancer) and papillomas have also been attributed to the modi cation of the pH of the secretory compartment (Kellokumpu et al. 2002).