Peroxisomes are dispensable for normal renal function.

Peroxisomes are highly abundant in proximal tubules where peroxisomal enzymes have been proposed to play an important role in a variety of metabolic and antioxidant functions. This hypothesis was supported by human genetic studies that identified mutations leading to peroxisomal biogenesis deficiency, resulting in severe multi-organ damage (Zellweger's spectrum disorders (ZSD)), including renal impairment. However, the role of proximal tubule peroxisomes in renal (patho)physiology remains uninvestigated. We addressed this question in mice with conditional ablation of peroxisomal biogenesis in the renal tubule. Our results demonstrate that renal tubular peroxisomes are dispensable for normal renal function and suggest that renal damage in ZSD patients is of extrarenal origin. Overall design: Peroxisome biogenesis in the renal tubule was disrupted through conditional inactivation of Pex5 encoding cytosolic peroxisome targeting signal 1 (PTS1) receptor essential for import of PTS1 motif-containing proteins into peroxisomes. The Pex5 deletion in the renal tubule of adult mice was induced by 2-week treatment with DOX of 8-week-old Pex5lox/lox/Pax8-rtTA/LC1 male and female mice. In parallel, the same DOX treatment was provided to their littermate controls (Pex5lox/lox mice). All experiments on adult mice were performed 4 weeks after the end of DOX treatment.