{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T08:46:09Z","timestamp":1768034769391,"version":"3.49.0"},"reference-count":56,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T00:00:00Z","timestamp":1663632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["325510"],"award-info":[{"award-number":["325510"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sigrid Juselius foundation","award":["325510"],"award-info":[{"award-number":["325510"]}]},{"name":"Finnish Foundation for Cardiovascular Research","award":["325510"],"award-info":[{"award-number":["325510"]}]},{"name":"Finnish Cultural Foundation","award":["325510"],"award-info":[{"award-number":["325510"]}]},{"name":"Paavo Nurmi Foundation","award":["325510"],"award-info":[{"award-number":["325510"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Transcriptional coactivator PGC-1\u03b1 is a main regulator of cardiac energy metabolism. In addition to canonical PGC-1\u03b11, other PGC-1\u03b1 isoforms have been found to exert specific biological functions in a variety of tissues. We investigated the expression patterns and the biological effects of the non-canonical isoforms in the heart. We used RNA sequencing data to identify the expression patterns of PGC-1\u03b1 isoforms in the heart. To evaluate the biological effects of the alternative isoform expression, we generated a transgenic mouse with cardiac-specific overexpression of PGC-1\u03b14 and analysed the cardiac phenotype with a wide spectrum of physiological and biophysical tools. Our results show that non-canonical isoforms are expressed in the heart, and that the main variant PGC-1\u03b14 is induced by \u03b2-adrenergic signalling in adult cardiomyocytes. Cardiomyocyte specific PGC-1\u03b14 overexpression in mice relieves the RE1-Silencing Transcription factor (REST)-mediated suppression of neuronal genes during foetal heart development. The resulting de-repression of REST target genes induces a cardiac phenotype with increased cellular energy consumption, resulting in postnatal dilated cardiomyopathy. These results propose a new concept for actions of the PGC-1\u03b1 protein family where activation of the Pgc-1\u03b1 gene, through its isoforms, induces a phenotype with concurrent supply and demand for cellular energy. These data highlight the biological roles of the different PGC-1\u03b1 isoforms, which should be considered when future therapies are developed.<\/jats:p>","DOI":"10.3390\/cells11192944","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T21:12:53Z","timestamp":1663708373000},"page":"2944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["PGC-1\u03b14 Interacts with REST to Upregulate Neuronal Genes and Augment Energy Consumption in Developing Cardiomyocytes"],"prefix":"10.3390","volume":"11","author":[{"given":"Tomi","family":"Tuomainen","sequence":"first","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0380-7403","authenticated-orcid":false,"given":"Nikolay","family":"Naumenko","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maija","family":"Mutikainen","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8236-2328","authenticated-orcid":false,"given":"Anastasia","family":"Shakirzyanova","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Sczelecki","sequence":"additional","affiliation":[{"name":"Institut de Recherches Cliniques de Montr\u00e9al, Montr\u00e9al, QC H2W 1R7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9838-1440","authenticated-orcid":false,"given":"Jennifer L.","family":"Estall","sequence":"additional","affiliation":[{"name":"Institut de Recherches Cliniques de Montr\u00e9al, Montr\u00e9al, QC H2W 1R7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1110-2606","authenticated-orcid":false,"given":"Jorge L.","family":"Ruas","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Exercise Physiology, Department of Physiology and Pharmacology, Biomedicum, Karolinska Institute, 17165 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pasi","family":"Tavi","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1210\/er.2006-0037","article-title":"Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism","volume":"27","author":"Handschin","year":"2006","journal-title":"Endocr. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1046\/j.1440-1681.2002.03655.x","article-title":"Transcriptional activation of energy metabolic switches in the developing and hypertrophied heart","volume":"29","author":"Lehman","year":"2002","journal-title":"Clin. Exp. Pharmacol. 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