{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:57:58Z","timestamp":1790269078410,"version":"4.1.0"},"reference-count":53,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T00:00:00Z","timestamp":1608249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie","award":["643051"],"award-info":[{"award-number":["643051"]}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["EFRE-0800978"],"award-info":[{"award-number":["EFRE-0800978"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"name":"H2020 Consortium NSC-Reconstruct","award":["874758"],"award-info":[{"award-number":["874758"]}]},{"name":"Young Researcher Program University Frankfurt","award":["SKS"],"award-info":[{"award-number":["SKS"]}]},{"name":"Young researcher funding from the IZKF W\u00fcrzburg","award":["Z3-24"],"award-info":[{"award-number":["Z3-24"]}]},{"name":"Open Access Publication Fund of the University of W\u00fcrzburg","award":["Open access"],"award-info":[{"award-number":["Open access"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>The main goal of the present study was the identification of cellular phenotypes in attention-deficit-\/hyperactivity disorder (ADHD) patient-derived cellular models from carriers of rare copy number variants (CNVs) in the PARK2 locus that have been previously associated with ADHD. Human-derived fibroblasts (HDF) were cultured and human-induced pluripotent stem cells (hiPSC) were reprogrammed and differentiated into dopaminergic neuronal cells (mDANs). A series of assays in baseline condition and in different stress paradigms (nutrient deprivation, carbonyl cyanide m-chlorophenyl hydrazine (CCCP)) focusing on mitochondrial function and energy metabolism (ATP production, basal oxygen consumption rates, reactive oxygen species (ROS) abundance) were performed and changes in mitochondrial network morphology evaluated. We found changes in PARK2 CNV deletion and duplication carriers with ADHD in PARK2 gene and protein expression, ATP production and basal oxygen consumption rates compared to healthy and ADHD wildtype control cell lines, partly differing between HDF and mDANs and to some extent enhanced in stress paradigms. The generation of ROS was not influenced by the genotype. Our preliminary work suggests an energy impairment in HDF and mDAN cells of PARK2 CNV deletion and duplication carriers with ADHD. The energy impairment could be associated with the role of PARK2 dysregulation in mitochondrial dynamics.<\/jats:p>","DOI":"10.3390\/jcm9124092","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T04:12:01Z","timestamp":1608523921000},"page":"4092","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Energy Metabolism Disturbances in Cell Models of PARK2 CNV Carriers with ADHD"],"prefix":"10.3390","volume":"9","author":[{"given":"Viola Stella","family":"Palladino","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, University Hospital, Goethe University, D-60528 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas G.","family":"Chiocchetti","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital Frankfurt, D-60528 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Frank","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, University Hospital, Goethe University, D-60528 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Haslinger","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital Frankfurt, D-60528 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhiannon","family":"McNeill","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, University Hospital, University of W\u00fcrzburg, D-97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Radtke","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatic Medicine, University Hospital, University of W\u00fcrzburg, D-97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0139-9143","authenticated-orcid":false,"given":"Andreas","family":"Till","sequence":"additional","affiliation":[{"name":"Institute of Reconstructive Neurobiology, LIFE &amp; BRAIN Center, University of Bonn Medical Faculty &amp; University Hospital Bonn, D-53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Haupt","sequence":"additional","affiliation":[{"name":"LIFE &amp; BRAIN GmbH, Cellomics Unit, D-53127 Bonn, Germany"},{"name":"Department 75, Transfer, University of Cologne, 50923 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Br\u00fcstle","sequence":"additional","affiliation":[{"name":"Institute of Reconstructive Neurobiology, LIFE &amp; BRAIN Center, University of Bonn Medical Faculty &amp; University Hospital Bonn, D-53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2954-4883","authenticated-orcid":false,"given":"Katharina","family":"G\u00fcnther","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology &amp; CMBI, University of Innsbruck, AT-6020 Innsbruck, Austria"},{"name":"Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University Salzburg, AT-5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Edenhofer","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology &amp; CMBI, University of Innsbruck, AT-6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Institute of Humane Genetics, LIFE &amp; BRAIN Center, University of Bonn Medical Faculty &amp; University Hospital Bonn, D-53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Reif","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, University Hospital, Goethe University, D-60528 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3057-6150","authenticated-orcid":false,"given":"Sarah","family":"Kittel-Schneider","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, University Hospital, Goethe University, D-60528 Frankfurt, Germany"},{"name":"Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, University Hospital, University of W\u00fcrzburg, D-97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1017\/S003329171100153X","article-title":"The lifetime impact of attention deficit hyperactivity disorder: Results from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC)","volume":"42","author":"Bernardi","year":"2012","journal-title":"Psychol. 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