2024
A synthetic agent ameliorates polycystic kidney disease by promoting apoptosis of cystic cells through increased oxidative stress
Fedeles B, Bhardwaj R, Ishikawa Y, Khumsubdee S, Krappitz M, Gubina N, Volpe I, Andrade D, Westergerling P, Staudner T, Campolo J, Liu S, Dong K, Cai Y, Rehman M, Gallagher A, Ruchirawat S, Croy R, Essigmann J, Fedeles S, Somlo S. A synthetic agent ameliorates polycystic kidney disease by promoting apoptosis of cystic cells through increased oxidative stress. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2317344121. PMID: 38241440, PMCID: PMC10823221, DOI: 10.1073/pnas.2317344121.Peer-Reviewed Original ResearchConceptsCyst cellsAutosomal dominant polycystic kidney diseaseMouse models of autosomal dominant polycystic kidney diseasePolycystic kidney diseaseModel of autosomal dominant polycystic kidney diseaseKidney diseaseDeveloped primersMitochondrial oxidative stressPathophysiology of autosomal dominant polycystic kidney diseaseOxidative stressInduce apoptosisMitochondrial respirationCystic cellsUp-regulating aerobic glycolysisHomozygous inactivationMonogenic causeDominant polycystic kidney diseaseAerobic glycolysisRenal replacement therapyApoptosisEnd-stage kidney diseaseAnti-tumor agentsAdult mouse modelChronic kidney diseaseAlkylate DNA
2019
Polycystin 2 regulates mitochondrial Ca2+ signaling, bioenergetics, and dynamics through mitofusin 2
Kuo IY, Brill AL, Lemos FO, Jiang JY, Falcone JL, Kimmerling EP, Cai Y, Dong K, Kaplan DL, Wallace DP, Hofer AM, Ehrlich BE. Polycystin 2 regulates mitochondrial Ca2+ signaling, bioenergetics, and dynamics through mitofusin 2. Science Signaling 2019, 12 PMID: 31064883, PMCID: PMC6855602, DOI: 10.1126/scisignal.aat7397.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulumPC2 knockdownMitochondrial CaCell culture modelKnockdown of Mfn2Polycystin-2 functionsHuman ADPKD kidneysAutosomal dominant polycystic kidney diseaseKey mitochondrial proteinsAberrant cell proliferationMitochondria-ER contactsCell proliferationER-mitochondrial interfaceKidney cystsIntimate functional relationshipNumerous fluid-filled cystsMitochondrial proteinsCyst-lining epithelial cellsMitofusin 2 expressionCulture modelPolycystin-2Knockdown cellsMitochondrial biogenesisMitofusin 2Mitochondrial respiration