Phase Separation in Kidney Diseases: Autosomal Dominant Polycystic Kidney Disease and Beyond.

Abstract

The formation of biomolecular condensates via phase separation has emerged as a fundamental principle underlying the spatiotemporal coordination of biological activities in cells. Aberrant biomolecular condensates often directly regulate key cellular process involved in the pathogenesis of human diseases, including kidney diseases. In this review, we summarize the physiological roles of phase separation and methodologies for phase separation studies. Taking autosomal dominant polycystic kidney disease as an example, we discuss recent advances toward elucidating the multiple mechanisms involved in kidney pathology arising from aberrant phase separation. We suggest that dysregulation of phase separation contributes to the pathogenesis of other important kidney diseases, including kidney injury and fibrosis. Phase separation provides a useful new concept to understand the mechanisms underlying kidney disease development. Targeting aberrant phase-separated condensates offers new therapeutic avenues for combating kidney diseases.