Metabolic reprogramming in polycystic kidney disease and other renal ciliopathies.

Primary cilia are solitary organelles formed by a microtubule-based skeleton protruding in a single copy on the surface of most cells. Alterations in their function cause a plethora of human conditions collectively called the ciliopathies. The kidney is frequently and severely affected in the ciliopathies, presenting with a spectrum of phenotypes. Cyst formation is a common trait of all renal ciliopathies. Besides this common manifestation, however, the renal ciliopathies present with profoundly different phenotypes, resulting in either polycystic kidney disease (PKD) or nephronophthisis (NPH) phenotypes. The past decade has seen a surge of studies highlighting metabolic reprogramming as a major feature of PKD, with a distinct involvement of mitochondrial dysfunction. This discovery has brought forward the development of novel therapeutic approaches. More recent evidence suggests that primary cilia modulate the mitochondrial production of energy in response to environmental cues. Here, we summarize the evidence available to date and propose a more general involvement of metabolic and mitochondrial alterations in the renal ciliopathies that might in principle help defining the profoundly different, and potentially opposite, manifestations observed.