{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:57:38Z","timestamp":1790805458945,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T00:00:00Z","timestamp":1639612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Research Foundation - Flanders","doi-asserted-by":"publisher","award":["KaN2018 1524519N"],"award-info":[{"award-number":["KaN2018 1524519N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by deficiency of polycystin-1 (PC1) or polycystin-2 (PC2). Altered autophagy has recently been implicated in ADPKD progression, but its exact regulation by PC1 and PC2 remains unclear. We therefore investigated cell death and survival during nutritional stress in mouse inner medullary collecting duct cells (mIMCDs), either wild-type (WT) or lacking PC1 (PC1KO) or PC2 (PC2KO), and human urine-derived proximal tubular epithelial cells (PTEC) from early-stage ADPKD patients with PC1 mutations versus healthy individuals. Basal autophagy was enhanced in PC1-deficient cells. Similarly, following starvation, autophagy was enhanced and cell death reduced when PC1 was reduced. Autophagy inhibition reduced cell death resistance in PC1KO mIMCDs to the WT level, implying that PC1 promotes autophagic cell survival. Although PC2 expression was increased in PC1KO mIMCDs, PC2 knockdown did not result in reduced autophagy. PC2KO mIMCDs displayed lower basal autophagy, but more autophagy and less cell death following chronic starvation. This could be reversed by overexpression of PC1 in PC2KO. Together, these findings indicate that PC1 levels are partially coupled to PC2 expression, and determine the transition from renal cell survival to death, leading to enhanced survival of ADPKD cells during nutritional stress.<\/jats:p>","DOI":"10.3390\/ijms222413511","type":"journal-article","created":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T11:27:36Z","timestamp":1639654056000},"page":"13511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Interdependent Regulation of Polycystin Expression Influences Starvation-Induced Autophagy and Cell Death"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6050-599X","authenticated-orcid":false,"given":"Jean-Paul","family":"Decuypere","sequence":"first","affiliation":[{"name":"Laboratory of Pediatrics, PKD Research Group, Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorien","family":"Van Giel","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatrics, PKD Research Group, Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium"},{"name":"Laboratory of Ion Channel Research, Biomedical Sciences Group, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Janssens","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatrics, PKD Research Group, Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium"},{"name":"Department of Nephrology, University Hospitals Brussels, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Somlo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA"},{"name":"Department of Genetics, Yale School of Medicine, New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqiang","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djalila","family":"Mekahli","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatrics, PKD Research Group, Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium"},{"name":"Department of Pediatric Nephrology, University Hospital of Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudi","family":"Vennekens","sequence":"additional","affiliation":[{"name":"Laboratory of Ion Channel Research, Biomedical Sciences Group, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium"},{"name":"VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"i679","DOI":"10.1136\/bmj.i679","article-title":"Autosomal dominant polycystic kidney disease","volume":"352","author":"Simms","year":"2016","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1681\/ASN.2007020155","article-title":"Autosomal dominant polycystic kidney disease: Time for a change?","volume":"18","author":"Chapman","year":"2007","journal-title":"J. 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