{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T11:07:03Z","timestamp":1785582423218,"version":"3.56.0"},"reference-count":89,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T00:00:00Z","timestamp":1690761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"the National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["1R21 MH118076"],"award-info":[{"award-number":["1R21 MH118076"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>HIV-associated cognitive dysfunction during combination antiretroviral therapy (cART) involves mitochondrial dysfunction, but the impact of contemporary cART on chronic metabolic changes in the brain and in latent HIV infection is unclear. We interrogated mitochondrial function in a human microglia (h\u03bcglia) cell line harboring inducible HIV provirus and in SH-SY5Y cells after exposure to individual antiretroviral drugs or cART, using the MitoStress assay. cART-induced changes in protein expression, reactive oxygen species (ROS) production, mitochondrial DNA copy number, and cellular iron were also explored. Finally, we evaluated the ability of ROS scavengers or plasmid-mediated overexpression of the antioxidant iron-binding protein, Fth1, to reverse mitochondrial defects. Contemporary antiretroviral drugs, particularly bictegravir, depressed multiple facets of mitochondrial function by 20\u201330%, with the most pronounced effects in latently infected HIV+ h\u03bcglia and SH-SY5Y cells. Latently HIV-infected h\u03bcglia exhibited upregulated glycolysis. Increases in total and\/or mitochondrial ROS, mitochondrial DNA copy number, and cellular iron accompanied mitochondrial defects in h\u03bcglia and SH-SY5Y cells. In SH-SY5Y cells, cART reduced mitochondrial iron\u2013sulfur-cluster-containing supercomplex and subunit expression and increased Nox2 expression. Fth1 overexpression or pre-treatment with N-acetylcysteine prevented cART-induced mitochondrial dysfunction. Contemporary cART impairs mitochondrial bioenergetics in h\u03bcglia and SH-SY5Y cells, partly through cellular iron accumulation; some effects differ by HIV latency.<\/jats:p>","DOI":"10.3390\/ijms241512242","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T09:22:38Z","timestamp":1690795358000},"page":"12242","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Contemporary Antiretroviral Therapy Dysregulates Iron Transport and Augments Mitochondrial Dysfunction in HIV-Infected Human Microglia and Neural-Lineage Cells"],"prefix":"10.3390","volume":"24","author":[{"given":"Harpreet","family":"Kaur","sequence":"first","affiliation":[{"name":"Department of Genomic Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige","family":"Minchella","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Alvarez-Carbonell","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Biology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeraja","family":"Purandare","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0917-3093","authenticated-orcid":false,"given":"Vijay K.","family":"Nagampalli","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6833-9049","authenticated-orcid":false,"given":"Daniel","family":"Blankenberg","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Hulgan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Gerschenson","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96844, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2900-094X","authenticated-orcid":false,"given":"Jonathan","family":"Karn","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Biology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddhesh","family":"Aras","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asha R.","family":"Kallianpur","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/nrneurol.2016.53","article-title":"HIV-associated neurocognitive disorder\u2014Pathogenesis and prospects for treatment","volume":"12","author":"Saylor","year":"2016","journal-title":"Nat. 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