Renal tubular peroxisomes are dispensable for normal kidney function

Area of Science:

• Cell Biology
• Organelle Function
• Renal Physiology

Background:

• Peroxisomes are vital organelles for metabolism.
• Loss of peroxisomes causes Zellweger's spectrum disorders (ZSD) with renal impairment.
• The specific role of kidney peroxisomes is unclear.

Purpose of the Study:

• To investigate the role of peroxisomes in renal function.
• To determine if peroxisomal dysfunction in renal tubules impacts kidney health.
• To explore metabolic adaptations in peroxisome-deficient kidney cells.

Main Methods:

• Conditional knockout (cKO) mouse model with peroxisome deficiency in renal tubules.
• Physiological and stereological analyses of kidney structure and function.
• Transcriptome and metabolome profiling to assess metabolic changes.
• High-fat diet challenge to evaluate kidney resilience.

Main Results:

• Conditional ablation of peroxisomes in renal tubules did not cause overt kidney dysfunction.
• Male cKO mice showed reduced body and kidney weights.
• Increased mitochondrial density and metabolic pathway reprogramming (glutathione, lipids) were observed.
• Compensated oxidative stress was suggested, but high-fat feeding did not worsen renal function.

Conclusions:

• Renal tubular peroxisomes are dispensable for maintaining normal kidney function.
• Observed renal impairments in ZSD patients likely originate from extrarenal factors.
• The kidney exhibits metabolic plasticity in the absence of peroxisomal function.