{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T07:46:06Z","timestamp":1762674366385,"version":"build-2065373602"},"reference-count":58,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,3,20]],"date-time":"2020-03-20T00:00:00Z","timestamp":1584662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000937","name":"Department of Education, Employment and Workplace Relations, Australian Government","doi-asserted-by":"publisher","award":["XX"],"award-info":[{"award-number":["XX"]}],"id":[{"id":"10.13039\/501100000937","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001778","name":"Deakin University","doi-asserted-by":"publisher","award":["XX"],"award-info":[{"award-number":["XX"]}],"id":[{"id":"10.13039\/501100001778","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010846","name":"Australian Mitochondrial Disease Foundation","doi-asserted-by":"publisher","award":["XX"],"award-info":[{"award-number":["XX"]}],"id":[{"id":"10.13039\/100010846","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1159795"],"award-info":[{"award-number":["GNT1159795"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004752","name":"State Government of Victoria","doi-asserted-by":"publisher","award":["XX"],"award-info":[{"award-number":["XX"]}],"id":[{"id":"10.13039\/501100004752","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The lack of effective treatments for mitochondrial disease has seen the development of new approaches, including those that aim to stimulate mitochondrial biogenesis to boost ATP generation above a critical disease threshold. Here, we examine the effects of the peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3) activator pioglitazone (PioG), in combination with deoxyribonucleosides (dNs), on mitochondrial biogenesis in cybrid cells containing &gt;90% of the m.3243A&gt;G mutation associated with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). PioG + dNs combination treatment increased mtDNA copy number and mitochondrial mass in both control (CON) and m.3243A&gt;G (MUT) cybrids, with no adverse effects on cell proliferation. PioG + dNs also increased mtDNA-encoded transcripts in CON cybrids, but had the opposite effect in MUT cybrids, reducing the already elevated transcript levels. Steady-state levels of mature oxidative phosphorylation (OXPHOS) protein complexes were increased by PioG + dNs treatment in CON cybrids, but were unchanged in MUT cybrids. However, treatment was able to significantly increase maximal mitochondrial oxygen consumption rates and cell respiratory control ratios in both CON and MUT cybrids. Overall, these findings highlight the ability of PioG + dNs to improve mitochondrial respiratory function in cybrid cells containing the m.3243A&gt;G MELAS mutation, as well as their potential for development into novel therapies to treat mitochondrial disease.<\/jats:p>","DOI":"10.3390\/ijms21062139","type":"journal-article","created":{"date-parts":[[2020,3,20]],"date-time":"2020-03-20T11:42:11Z","timestamp":1584704531000},"page":"2139","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Pioglitazone and Deoxyribonucleoside Combination Treatment Increases Mitochondrial Respiratory Capacity in m.3243A&gt;G MELAS Cybrid Cells"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8575-3551","authenticated-orcid":false,"given":"Harrison J.","family":"Burgin","sequence":"first","affiliation":[{"name":"School of Life and Environmental Sciences, Faculty of Science, Engineering and Built Environment, Deakin University, Geelong 3216, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1528-5964","authenticated-orcid":false,"given":"M. Isabel G.","family":"Lopez Sanchez","sequence":"additional","affiliation":[{"name":"Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria 3002, Australia"},{"name":"Ophthalmology, University of Melbourne, Department of Surgery Melbourne, Victoria 3000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig M.","family":"Smith","sequence":"additional","affiliation":[{"name":"School of Medicine, Faculty of Health, Deakin University, Geelong 3216, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian A.","family":"Trounce","sequence":"additional","affiliation":[{"name":"Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria 3002, Australia"},{"name":"Ophthalmology, University of Melbourne, Department of Surgery Melbourne, Victoria 3000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7508-1800","authenticated-orcid":false,"given":"Matthew","family":"McKenzie","sequence":"additional","affiliation":[{"name":"School of Life and Environmental Sciences, Faculty of Science, Engineering and Built Environment, Deakin University, Geelong 3216, Australia"},{"name":"Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Melbourne 3168, Australia"},{"name":"Department of Molecular and Translational Science, Monash University, Melbourne 3168, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1002\/ana.24362","article-title":"Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease","volume":"77","author":"Gorman","year":"2015","journal-title":"Ann. 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