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This review explains why the mitochondrial context matters: mtDNA has higher platinum affinity than nDNA, and mtDNA mutations can alter chemosensitivity via DNA damage responses, metabolic shifts, ROS homeostasis, and mitochondrial dynamics. Retrograde mtDNA-to-nucleus signaling reorganizes nuclear transcription, while intercellular mitochondrial transfer further modulates chemotherapy effectiveness, making mitochondria a promising therapeutic target.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/targeting-mitochondria-a-novel-approach-for-treating-platinum-resistant-ovarian-cancer/332668/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/targeting-mitochondria-a-novel-approach-for-treating-platinum-resistant-ovarian-cancer/332668.png","ImageObject",300,407,{"name":92,"@type":93},"Sage","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why does platinum-based chemotherapy often fail in ovarian cancer?","Question",{"text":112,"@type":113},"After initial treatment, many patients relapse and develop platinum resistance. 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Journal of Translational Medicine (2024) 22:968  \n[https://doi.org/10.1186/s12967-024-05770-y](https://doi.org/10.1186/s12967-024-05770-y)  \nJournal of Translational Medicine  \nREVIEW Open Access  \nTargeting mitochondria: a novel approach  for treating platinum-resistant ovarian cancer  \nXin Cui 1†, Juan Xu 1,2*† and Xuemei Jia 1,2*  \nAbstract  \nOvarian cancer is a prevalent gynecologic malignancy with the second-highest mortality rate among gynecologic malignancies. Platinum-based chemotherapy is the first-line treatment for ovarian cancer; however, a majority of patients with ovarian cancer experience relapse and develop platinum resistance following initial treatment. Despite extensive research on the mechanisms of platinum resistance at the nuclear level, the issue of platinum resistance in ovarian cancer remains largely unresolved. It is noteworthy that mitochondrial DNA (mtDNA) exhibits higher affinity for platinum compared to nuclear DNA (nDNA) . Mutations in mtDNA can modulate tumor chemosensitivity through various mechanisms, including DNA damage responses, shifts in energy metabolism, maintenance of Reactive Oxygen Species (ROS) homeostasis, and alterations in mitochondrial dynamics. Concurrently, retrograde signals produced by mtDNA mutations and their subsequent cascades establish communication with the nucleus, leading to the reorganization of the nuclear transcriptome and governing the transcription of genes and signaling pathways associated with chemoresistance. Furthermore, mitochondrial translocation among cells emerges as a crucial factor influencing the effectiveness of chemotherapy in ovarian cancer. This review aims to explore the role and mechanism of mitochondria in platinum resistance, with a specific focus on mtDNA mutations and the resulting metabolic reprogramming, ROS regulation, changes in mitochondrial dynamics, mitochondria-nucleus communication, and mitochondrial transfer.  \nHighlights  \n• Directly targeting mitochondria is one of the main mechanisms by which platinum induces apoptosis in tumor cells.  \n• mtDNA mutations occur frequently in ovarian cancer and significantly contribute to platinum resistance.  \n• The metabolic heterogeneity induced by mtDNA mutations can directly drive platinum resistance in ovarian cancer cells.  \n• Targeting mitochondria could be a novel approach for platinum-resistant ovarian cancer.  \nKeywords Mitochondria, Platinum resistance, Mitochondria DNA (mtDNA), Metabolic reprogramming, Mitochondrial dynamics, Mitochondria-nucleus communication, Mitochondria transfer  \n†Xin Cui and Juan Xu contributed equally to this work.  \n*Correspondence:  \nJuan Xu [xujuannj@njmu.edu.cn](xujuannj@njmu.edu.cn)[ ](xujuannj@njmu.edu.cn)Xuemei Jia [xmjia@njmu.edu.cn](xmjia@njmu.edu.cn)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://](http://)[ ](http://)[creativecommons.org/l](creativecommons.org/l)icenses/by-nc-nd/4.0/.  \nCui et al. Journal of Translational Medicin","cbCaifVvYIC1WkbB","https://ap.wps.com/l/cbCaifVvYIC1WkbB","pdf",3348810,13,"English","# Abstract\n# Highlights\n# Keywords\n# Introduction","[{\"question\":\"Why does platinum-based chemotherapy often fail in ovarian cancer?\",\"answer\":\"After initial treatment, many patients relapse and develop platinum resistance. The molecular basis remains incompletely resolved despite extensive study of nuclear-level mechanisms.\"},{\"question\":\"How do mitochondrial DNA (mtDNA) mutations contribute to platinum resistance?\",\"answer\":\"mtDNA mutations can modulate tumor chemosensitivity through mechanisms such as DNA damage responses, altered energy metabolism, ROS homeostasis changes, and shifts in mitochondrial dynamics.\"},{\"question\":\"What mitochondrial-related mechanisms are discussed as new therapeutic targets?\",\"answer\":\"The review highlights direct targeting of mitochondria as a way platinum can induce apoptosis, mtDNA mutation-driven metabolic and signaling reprogramming, mitochondrial-nucleus communication, and mitochondrial transfer between cells that can affect chemotherapy effectiveness.\"}]","Targeting mitochondria: a novel approach for treating platinum-resistant ovarian cancer | PDF",1789999027,33]