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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,7,28]]},"abstract":"<jats:p>\n                    Mitochondrial biogenesis is a fundamental process that ensures energy supply and supports steroidogenesis in ovarian cells. Lactate has recently been identified as a signaling metabolite that promotes mitochondrial biogenesis; however, the underlying regulatory mechanisms remain poorly defined. Here, we identify Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90\u03b1) lactylation as a key mediator that links glycolytic metabolism to mitochondrial function. Specifically, lactylation of HSP90\u03b1 at K58 recruits ULK1, thereby enhancing phosphorylation at S39; lactylation at K616 prevents CDK5-mediated phosphorylation at S596. This dual regulation facilitates the nuclear translocation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1\u03b1) and its isoform LRPGC1, which activate NRF1\/2-dependent transcription of mitochondrial biogenesis genes, such as\n                    <jats:italic toggle=\"yes\">Tfb1m<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">Tfb2m<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">Tfam<\/jats:italic>\n                    . Functionally, mitochondrial mass expansion both enhances cellular energy metabolism and promotes cholesterol import into mitochondria, thereby driving estrogen biosynthesis. Together, these findings reveal a lactate\u2013HSP90\u03b1\u2013PGC1\u03b1\/LRPGC1 axis that metabolically couples glycolysis to mitochondrial biogenesis and reproductive hormone production, providing insights into the epigenetic regulation of follicular development.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2528979123","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T18:00:45Z","timestamp":1784656845000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["HSP90\u03b1 lactylation orchestrates PGC1\u03b1 and LRPGC1 nuclear translocation driving mitochondrial biogenesis"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5503-1384","authenticated-orcid":false,"given":"Gang","family":"Wu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05td3s095","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Genetic 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