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How cells balance lipid storage and mitochondrial oxidative capacity is poorly understood. Here we identify the lipid droplet protein Perilipin 5 as a catecholamine-triggered interaction partner of PGC-1\u03b1. We report that during catecholamine-stimulated lipolysis, Perilipin 5 is phosphorylated by protein kinase A and forms transcriptional complexes with PGC-1\u03b1 and SIRT1 in the nucleus. Perilipin 5 promotes PGC-1\u03b1 co-activator function by disinhibiting SIRT1 deacetylase activity. We show by gain-and-loss of function studies in cells that nuclear Perilipin 5 promotes transcription of genes that mediate mitochondrial biogenesis and oxidative function. We propose that Perilipin 5 is an important molecular link that couples the coordinated catecholamine activation of the PKA pathway and of lipid droplet lipolysis with transcriptional regulation to promote efficient fatty acid catabolism and prevent mitochondrial dysfunction.<\/jats:p>","DOI":"10.1038\/ncomms12723","type":"journal-article","created":{"date-parts":[[2016,8,24]],"date-time":"2016-08-24T10:56:42Z","timestamp":1472036202000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":159,"title":["Nuclear Perilipin 5 integrates lipid droplet lipolysis with PGC-1\u03b1\/SIRT1-dependent transcriptional regulation of mitochondrial function"],"prefix":"10.1038","volume":"7","author":[{"given":"Violeta I.","family":"Gallardo-Montejano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geetu","family":"Saxena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Kusminski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaofeng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7645-631X","authenticated-orcid":false,"given":"John L.","family":"McAfee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Hahner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Hoch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Dubinsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vihang A.","family":"Narkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6018-9579","authenticated-orcid":false,"given":"Perry E.","family":"Bickel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,8,24]]},"reference":[{"key":"BFncomms12723_CR1","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1210\/en.2007-1713","volume":"149","author":"NA Ducharme","year":"2008","unstructured":"Ducharme, N. 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