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The persistent failure of multiline chemotherapy, and significant tumor heterogeneity, has made it challenging to improve outcomes. A target of increasing interest is the mitochondrion because of its essential role in critical cellular functions, and the significance of metabolic adaptation in chemoresistance. This review describes mitochondrial processes, including metabolic reprogramming, mitochondrial transfer and mitochondrial dynamics in ovarian cancer progression and chemoresistance. The effect of malignant ascites, or excess peritoneal fluid, on mitochondrial function is discussed. The role of photodynamic therapy (PDT) in overcoming mitochondria\u2010mediated resistance is presented. PDT, a photochemistry\u2010based modality, involves the light\u2010based activation of a photosensitizer leading to the production of short\u2010lived reactive molecular species and spatiotemporally confined photodamage to nearby organelles and biological targets. The consequential effects range from subcytotoxic priming of target cells for increased sensitivity to subsequent treatments, such as chemotherapy, to direct cell killing. This review discusses how PDT\u2010based approaches can address key limitations of current treatments. Specifically, an overview of the mechanisms by which PDT alters mitochondrial function, and a summary of preclinical advancements and clinical PDT experience in ovarian cancer are provided.<\/jats:p>","DOI":"10.1111\/php.13723","type":"journal-article","created":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T03:24:40Z","timestamp":1663557880000},"page":"448-468","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Photochemical Targeting of Mitochondria to Overcome Chemoresistance in Ovarian Cancer\n                    <sup>\u2020<\/sup>"],"prefix":"10.1111","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6112-1290","authenticated-orcid":false,"given":"Brittany P.","family":"Rickard","sequence":"first","affiliation":[{"name":"Curriculum in Toxicology &amp; Environmental Medicine, University of North Carolina School of Medicine University of North Carolina at Chapel Hill  Chapel Hill NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Overchuk","sequence":"additional","affiliation":[{"name":"Joint Department of Biomedical Engineering University of North Carolina at Chapel Hill and North Carolina State University  Chapel Hill NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Girgis","family":"Obaid","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Texas at Dallas  Richardson TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa Kemal","family":"Ruhi","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering Bo\u011fazi\u00e7i University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Utkan","family":"Demirci","sequence":"additional","affiliation":[{"name":"Department of Radiology, Canary Center at Stanford for Cancer Early Detection Stanford University School of Medicine  Palo Alto CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne E.","family":"Fenton","sequence":"additional","affiliation":[{"name":"Curriculum in Toxicology &amp; Environmental Medicine, University of North Carolina School of Medicine University of North Carolina at Chapel Hill  Chapel Hill NC"},{"name":"Mechanistic Toxicology Branch, Division of the National Toxicology Program National Institute of Environmental Health Sciences  Research Triangle Park NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine H.","family":"Santos","sequence":"additional","affiliation":[{"name":"Mechanistic Toxicology Branch, Division of the National Toxicology Program National Institute of Environmental Health Sciences  Research Triangle Park NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3221-9299","authenticated-orcid":false,"given":"David","family":"Kessel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Wayne State University School of Medicine  Detroit MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9673-4700","authenticated-orcid":false,"given":"Imran","family":"Rizvi","sequence":"additional","affiliation":[{"name":"Curriculum in Toxicology &amp; Environmental Medicine, University of North Carolina School of Medicine University of North Carolina at Chapel Hill  Chapel Hill NC"},{"name":"Joint Department of Biomedical Engineering University of North Carolina at Chapel Hill and North Carolina State University  Chapel Hill NC"},{"name":"Lineberger Comprehensive Cancer Center University of North Carolina School of Medicine  Chapel Hill NC"},{"name":"Center for Environmental Health and Susceptibility University of North Carolina at Chapel Hill  Chapel Hill NC"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,10,19]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21708"},{"key":"e_1_2_6_4_1","volume-title":"Ovarian Cancer: Key Stats","author":"Globocan","year":"2020"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.5732\/cjc.014.10274"},{"key":"e_1_2_6_6_1","first-page":"288","article-title":"Recurrent epithelial ovarian cancer: An update on treatment","volume":"27","author":"Foley O. 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