Targeting mitochondrial homeostasis as a cancer treatment strategy - current status and future prospects

Sep 22, 2026

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Mitochondria regulate metabolism and coordinate with other organelles, and mitochondrial dysfunction drives disease onset and progression, including cancer. In tumor cells, metabolic reprogramming, defective mitochondrial quality control, and mitochondrial DNA damage connect to tumor initiation, development, and metastasis. The review also covers how altered mitochondrial function in the tumor microenvironment, such as CD8+ T cells, supports cancer progression, and summarizes mitochondria-targeted therapeutic updates and translational gaps while outlining future directions.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages33

Reading Time1 h 23 min

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Background

Mitochondria as regulators in cancer progression

Mitochondrial quality control and homeostasis mechanisms

Zhong et al. Molecular Cancer (2026) 25:38 Molecular Cancer [https://doi.org/10.1186/s12943-026-02571-3](https://doi.org/10.1186/s12943-026-02571-3) REVIEW Open Access Targeting mitochondrial homeostasis asa cancer treatment strategy: current status and future prospects Honglin Zhong1,2†, Renjie Pan1,3†, Yuzhen Ouyang1,4†, Tengfei Xiao1, Wangning Gu1, Hongmin Yang1, Hui Wang1, Hucheng Li1*, Tianfang Peng1* and Pan Chen1* Abstract Mitochondria are central to health and disease by precisely regulating metabolism and interacting closely with other organelles. Mitochondrial dysfunction contributes to the initiation and development of numerous diseases, including cancer. In cancer cells, metabolic reprogramming, impaired mitochondrial quality control, and mitochondrial DNA damage are linked to tumor initiation, development, and metastasis. Dysregulated mitochondrial function in cells within the tumor microenvironment, such as CD8 + T cells, also promotes cancer progression. Therapeutic approaches targeting mitochondria range from dietary interventions to small-molecule drugs aimed at restoring mitochondrial dysfunction. In this review, we summarize the relationships between mitochondrial dysfunction and cancer from the perspectives of metabolism, quality control, mitochondrial DNA stability, ion homeostasis, and the tumor microenvironment. We also provide updates on mitochondria-targeted therapies, highlighting key translational gaps from bench to bedside. Finally, we discuss future directions for mitochondria-targeted cancer therapy, emphasizing mitochondrial homeostasis as a critical target for improving therapeutic outcomes. Keywords Mitochondrial Homeostasis, Cancer Metabolism Reprograming, Mitochondrial-Targeted Therapies, Tumor Microenvironment, Mitochondrial DNA (mtDNA) Damage †Honglin Zhong, Renjie Pan and Yuzhen Ouyang contributed equally to this article. *Correspondence: Hucheng Li [Lihucheng@hnca.org.cn](Lihucheng@hnca.org.cn)[ ](Lihucheng@hnca.org.cn)Tianfang Peng [Pengtianfang@hnca.org.cn](Pengtianfang@hnca.org.cn)[ ](Pengtianfang@hnca.org.cn)Pan Chen[chenpan08@csu.edu.cn](chenpan08@csu.edu.cn) 1Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283Th Tongzipo Road, Changsha 410031, Hunan Province, China 2Department of Urology, Xiangya Hospital, Central South University, 87Th Xiangya Road, Changsha 410008, Hunan Province, China 3Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, 87Th Xiangya Road, Changsha 410008, Hunan Province, China 4Department of Neurology, Xiangya Hospital, Central South University, 87Th Xiangya Road, Changsha 410008, Hunan Province, China © The Author(s) 2026. 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://creati](http://creati)[vecommons.org/licenses/by-nc-nd/4.0/](vecommons.org/licenses/by-nc-nd/4.0/.)[.](vecommons.org/licenses/by-nc-nd/4.0/.) Zhong et al. Molecular Cancer (2026) 25:38 Background Cancer remains a leading cause of mortality worldw

FAQs

How does mitochondrial dysfunction contribute to cancer development?

Mitochondrial dysfunction contributes to cancer initiation and progression through links to metabolic reprogramming, impaired mitochondrial quality control, and mitochondrial DNA damage.

What roles does mitochondrial homeostasis play in cancer cells and the tumor microenvironment?

Mitochondrial homeostasis supports cancer progression by regulating key functions in tumor cells and by dysregulating cellular functions in microenvironment components such as CD8+ T cells.

What kinds of therapies target mitochondria for cancer treatment?

Therapeutic strategies range from dietary interventions to small-molecule drugs designed to restore mitochondrial dysfunction, alongside updates on mitochondria-targeted approaches.

Sep 22, 2026

Uploaded by Ezra