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However, the precise role of mitochondrial respiration in cardiomyocyte hypertrophy is unclear. Phenylephrine (PE) treatment of rat neonatal H9c2 cardiomyocytes promotes significant hypertrophy with decreased mitochondrial oxygen consumption rate (OCR), membrane potential, respiratory subunit NDUFB8, UQCRC2 and ATP5A (ATP5F1A) expression, and accumulation of reactive oxygen species (ROS). Surprisingly, a 60% reduction in cell survival was observed in PE-treated cells relative to control cells when grown under the respiratory-proficient galactose medium. To revert H9c2 hypertrophy and increase survival, we performed a screening with compounds that boost mitochondrial OCR and scavenge ROS, and identified pyruvate plus uridine as the best hit. As corroboration of the in vitro study, supplementation of pyruvate plus uridine significantly prevented PE-induced cardiac hypertrophy, pericardial edema and bradycardia symptoms in zebrafish embryos. Moreover, pyruvate plus uridine decreased the ventricular and atrial area in cardiomyocyte-specific GFP transgenic Tg (myl7:HRAS-EGFP) lines. Using in vitro and in vivo models, we show that boosting of mitochondrial respiration through pyruvate supplementation and scavenging ROS through uridine supplementation jointly ameliorate cardiac hypertrophy and bradycardia symptoms.<\/jats:p>","DOI":"10.1242\/jcs.263653","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T08:19:53Z","timestamp":1745482793000},"source":"Crossref","is-referenced-by-count":5,"title":["Pyruvate plus uridine augments mitochondrial respiration and prevents cardiac hypertrophy in zebrafish and H9c2 cells"],"prefix":"10.1242","volume":"138","author":[{"given":"Soumyajit","family":"Mukherjee","sequence":"first","affiliation":[{"name":"University of Calcutta 1 Department of Biochemistry , , 35, Ballygunge Circular Road, Kolkata 700019 ,","place":["India"]},{"name":"Indian Institute of Science 2 Department of Biochemistry , , Bangalore 560012 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shreya","family":"Das","sequence":"additional","affiliation":[{"name":"Jadavpur University 3 Department of Life Science and Biotechnology , , Kolkata 700032 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Surajit","family":"Das","sequence":"additional","affiliation":[{"name":"University of Calcutta 1 Department of Biochemistry , , 35, Ballygunge Circular Road, Kolkata 700019 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samudra","family":"Gupta","sequence":"additional","affiliation":[{"name":"S.N. Pradhan Centre for Neurosciences, University of Calcutta 4 , 35, Ballygunge Circular Road, Kolkata 700019 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subhra Prakash","family":"Hui","sequence":"additional","affiliation":[{"name":"S.N. 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