{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:04:14Z","timestamp":1790391854152,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,22]]},"group-title":"Cell Biology","reference-count":37,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"id":[{"id":"https:\/\/ror.org\/02v80fc35","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Institutes of Health","award":["NIH\/NIA T32AG066574"],"award-info":[{"award-number":["NIH\/NIA T32AG066574"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Mitochondrial transplantation has recently emerged as an alternative treatment for cardiovascular disease (CVD), aimed at increasing mitochondrial number and improving mitochondrial function. Though mitochondrial dysfunction is a key factor in the development of right ventricular hypertrophy\/failure, the effects of mitochondrial transplantation on disease mitigation have been largely unexplored. Therefore, this\n                  <jats:italic>in vitro<\/jats:italic>\n                  study aimed to determine whether the transplantation of exogenous L6 myotube mitochondria mitigates negative outcomes in H9C2 cardiomyocytes that were stimulated to hypertrophy with phenylephrine. Control (CTL), control with mitochondrial transplantation (MitoTx), Phenylephrine only (Phe-only), and phenylephrine with mitochondrial transplantation (Phe+MitoTx) treatments were evaluated. Pilot experiments indicated mitochondrial transplantation into healthy cardiomyocytes acutely increased Complex I-linked oxidative phosphorylation (OXPHOS) capacity (p=0.005) and maximal respiratory capacity (p=0.022) within 24 hours, and these data alongside microscopic evidence of fluorescently labeled L6 mitochondria in H9C2 cardiomyocytes suggested successful transplantation. Regarding treatment comparisons, Phe-only showed a significant increase in cell area (p&lt;0.05), while Phe+MitoTx blunted the hypertrophic cardiomyocyte response. Consistent with these results, proteomic analysis of 4,806 proteins showed that transplantation enriched the mitochondrial proteome, impacting pathways including OXPHOS, respiration, fatty acid and amino acid metabolism, while suppressing extracellular matrix remodeling and de-differentiation signatures. This response was observed in healthy and phenylephrine-stressed cardiomyocytes. In conclusion, our\n                  <jats:italic>in vitro<\/jats:italic>\n                  data indicates that transplantation of L6 skeletal muscle mitochondria mitigates negative effects induced by phenylephrine in H9C2 cardiomyocytes. However, more rigorous\n                  <jats:italic>in vivo<\/jats:italic>\n                  studies are needed to determine if this is a suitable approach for disease mitigation.\n                <\/jats:p>","DOI":"10.64898\/2026.09.21.753229","type":"posted-content","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:15:27Z","timestamp":1790122527000},"source":"Crossref","is-referenced-by-count":0,"title":["Exogenous L6 myotube mitochondrial transplantation attenuates hypertrophy and elicits a unique proteomic signature in phenylephrine-treated H9C2 cardiomyocytes"],"prefix":"10.64898","author":[{"given":"Nicholas J.","family":"Kontos","sequence":"first","affiliation":[{"name":"School of Kinesiology, Auburn University, Auburn, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"George J.","family":"Kontos","sequence":"additional","affiliation":[{"name":"School of Kinesiology, Auburn University, Auburn, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dustyn T.","family":"Lewis","sequence":"additional","affiliation":[{"name":"School of Kinesiology, Auburn University, Auburn, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel C.","family":"Norton","sequence":"additional","affiliation":[{"name":"School of Kinesiology, Auburn University, Auburn, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley A.","family":"Ruple","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Washington Medicine, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas N.","family":"Kavazis","sequence":"additional","affiliation":[{"name":"School of Kinesiology, Auburn University, Auburn, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren T.","family":"Beck","sequence":"additional","affiliation":[{"name":"School of Kinesiology, Auburn University, Auburn, AL, USA"},{"name":"Edward Via College of Osteopathic Medicine-Auburn Campus, Auburn, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa D.","family":"Boersma","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Auburn University, Auburn, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher B.","family":"Mobley","sequence":"additional","affiliation":[{"name":"School of Kinesiology, Auburn University, Auburn, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle J.","family":"McCullough","sequence":"additional","affiliation":[{"name":"Edward Via College of Osteopathic Medicine-Auburn Campus, Auburn, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Ismaeel","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Roberts","sequence":"additional","affiliation":[{"name":"School of Kinesiology, Auburn University, Auburn, AL, USA"},{"name":"Edward Via College of Osteopathic Medicine-Auburn Campus, Auburn, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092519550552000_2026.09.21.753229v1.1","doi-asserted-by":"crossref","unstructured":"Sonaglioni A , Lombardo M , Gramaglia GF , Nicolosi GL , Lucidi A , Baravelli M , et al. 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