{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:17:15Z","timestamp":1791407835948,"version":"4.3.3"},"reference-count":50,"publisher":"American Society for Clinical Investigation","issue":"8","license":[{"start":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T00:00:00Z","timestamp":1596499200000},"content-version":"vor","delay-in-days":474,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01-DK095072"],"award-info":[{"award-number":["R01-DK095072"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,4,18]]},"abstract":"<jats:p>\n                    Because injured mitochondria can accelerate cell death through the elaboration of oxidative free radicals and other mediators, it is striking that proliferator \u03b3 coactivator 1-\u03b1 (PGC1\u03b1), a stimulator of increased mitochondrial abundance, protects stressed renal cells instead of potentiating injury. Here, we report that PGC1\u03b1\u2019s induction of lysosomes via transcription factor EB (TFEB) may be pivotal for kidney protection. CRISPR and stable gene transfer showed that PGC1\u03b1-KO tubular cells were sensitized to the genotoxic stressor cisplatin, whereas Tg cells were protected. The biosensor mitochondrial-targeted Keima (mtKeima) unexpectedly revealed that cisplatin blunts mitophagy both in cells and mice. PGC1\u03b1 and its downstream mediator NAD\n                    <jats:sup>+<\/jats:sup>\n                    counteracted this effect. PGC1\u03b1 did not consistently affect known autophagy pathways modulated by cisplatin. Instead RNA sequencing identified coordinated regulation of lysosomal biogenesis via TFEB. This effector pathway was sufficiently important that inhibition of TFEB or lysosomes unveiled a striking harmful effect of excess PGC1\u03b1 in cells and conditional mice. These results uncover an unexpected effect of cisplatin on mitophagy and PGC1\u03b1\u2019s reliance on lysosomes for kidney protection. Finally, the data illuminate TFEB as a potentially novel target for renal tubular stress resistance.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.126749","type":"journal-article","created":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T12:08:20Z","timestamp":1552565300000},"source":"Crossref","is-referenced-by-count":51,"title":["TFEB-driven lysosomal biogenesis is pivotal for PGC1\u03b1-dependent renal stress resistance"],"prefix":"10.1172","volume":"4","author":[{"given":"Matthew R.","family":"Lynch","sequence":"first","affiliation":[{"name":"Division of Nephrology,"},{"name":"Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1114-0984","authenticated-orcid":true,"given":"Mei T.","family":"Tran","sequence":"additional","affiliation":[{"name":"Division of Nephrology,"},{"name":"Department of Medicine, Beth 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