{"doi":"10.34067/kid.0000962021","title":"Pkd1 Mutation Has No Apparent Effects on Peroxisome Structure or Lipid Metabolism","abstract":"Key Points Although fatty acid (FA) oxidation defects have been reported in polycystic kidney disease (PKD), no studies have examined whether peroxisomes contribute to the abnormalities. We investigated peroxisome biogenesis and FA metabolism in autosomal dominant PKD models and tested whether polycystin-1 colocalized with peroxisome proteins. Our studies show that loss of Pkd1 does not disrupt peroxisome biogenesis nor peroxisome-dependent FA metabolism. Background Multiple studies of tissue and cell samples from patients and preclinical models of autosomal dominant polycystic kidney disease report abnormal mitochondrial function and morphology and suggest metabolic reprogramming is an intrinsic feature of this disease. Peroxisomes interact with mitochondria physically and functionally, and congenital peroxisome biogenesis disorders can cause various phenotypes, including mitochondrial defects, metabolic abnormalities, and renal cysts. We hypothesized that a peroxisomal defect might contribute to the metabolic and mitochondrial impairments observed in autosomal dominant polycystic kidney disease. Methods Using control and Pkd1−/− kidney epithelial cells, we investigated peroxisome abundance, biogenesis, and morphology by immunoblotting, immunofluorescence, and live cell imaging of peroxisome-related proteins and assayed peroxisomal specific β -oxidation. We further analyzed fatty acid composition by mass spectrometry in kidneys of Pkd1fl/fl;Ksp-Cre mice. We also evaluated peroxisome lipid metabolism in published metabolomics datasets of Pkd1 mutant cells and kidneys. Lastly, we investigated if the C terminus or full-length polycystin-1 colocalize with peroxisome markers by imaging studies. Results Peroxisome abundance, morphology, and peroxisome-related protein expression in Pkd1−/− cells were normal, suggesting preserved peroxisome biogenesis. Peroxisomal β -oxidation was not impaired in Pkd1−/− cells, and there was no obvious accumulation of very-long-chain fatty acids in kidneys of mutant mice. Reanalysis of published datasets provide little evidence of peroxisomal abnormalities in independent sets of Pkd1 mutant cells and cystic kidneys, and provide further evidence of mitochondrial fatty acid oxidation defects. Imaging studies with either full-length polycystin-1 or its C terminus, a fragment previously shown to go to the mitochondria, showed minimal colocalization with peroxisome markers restricted to putative mitochondrion-peroxisome contact sites. Conclusions Our studies showed that loss of Pkd1 does not disrupt peroxisome biogenesis nor peroxisome-dependent fatty acid metabolism.","journal":"Kidney360","year":2021,"id":211213,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.955,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":413446,"name":"Luís F. Menezes","orcid":"0000-0003-2225-168X","position":1,"is_corresponding":false},{"id":800151,"name":"Fang Zhou","orcid":"0000-0003-0189-3392","position":2,"is_corresponding":false},{"id":231167,"name":"Hongyi Cai","orcid":"0000-0002-8021-8493","position":3,"is_corresponding":false},{"id":231170,"name":"Peter J. Walter","orcid":"0000-0001-8571-398X","position":4,"is_corresponding":false},{"id":800626,"name":"H. Martin Garraffo","orcid":null,"position":5,"is_corresponding":false},{"id":246923,"name":"Gregory G. Germino","orcid":"0000-0002-3609-5588","position":6,"is_corresponding":false},{"id":413445,"name":"Takeshi Terabayashi","orcid":"0000-0001-7102-784X","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:52:16.049481Z","pmid":"35372986","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}