Role of Mammalian Aquaporin inside the Cell

Progress of the research on mammalian intracellular aquaporins (AQP) in the past 13 years is updated from our previous review. Despite the limited modalities of selectivity that are mostly based on charge exclusion and size selection through a couple of selectivity filters, a variety of solutes other than water are conducted through AQP such as glycerol, ammonia, urea, arsenic, silicon, H₂O₂ and even gas molecules including CO₂, O₂, NH₃, and NO with some controversies. Previous research interest in AQP was orientated toward water homeostasis assumed by the name, which is now shifting toward cellular metabolism and signaling. The initial name, MIP family, may be more appropriate to call this channel family especially for intracellular AQP functioning beyond as a water channel. For example, the functional identification of AQP11 as a H₂O₂-permeating peroxiporin (PXP) at the endoplasmic reticulum (ER) has expanded the role of AQP to regulate intracellular H₂O₂ homeostasis to prevent ER stress. In view of an extensive repertoire of MIP family, the diversity and nature of biologically relevant permeating solutes will be more extensive especially for intracellular AQP. This review focuses on the emerging function of intracellular AQP as PXP. Clarifying the full spectrum of functional roles and regulatory pathways of intracellular AQP will lead to new therapeutic strategies for diseases such as nephropathy, obesity, and diabetes.