Mitochondria at the Intersections of RNA Modifications and Metabolism Reprogramming: Implications in Cell Death, Tumor Microenvironment, and Immunotherapy

Sep 30, 2026

Uploaded by Terk

Mitochondria coordinate essential cellular functions, including energy production, metabolic regulation, programmed cell death, and signal transduction, making them central to many disease processes. RNA modifications act as influential posttranscriptional regulators of gene expression and increasingly shape mitochondrial activity. Evidence links RNA modifications to oxidative phosphorylation, regulated cell death such as cuproptosis, and antitumor immunity. This Review compiles key RNA modifications and small-molecule inhibitors affecting mitochondrial function, detailing roles in glucose metabolism, regulated death, and mitochondrial dynamics, and mapping how these pathways inform therapeutic targets for improved immunotherapy outcomes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages38

Reading Time1 h 36 min

AccessFree to download

Abstract

Keywords

Background

Mitochondria in cellular metabolism and regulated cell death

Mitochondria-related tumor microenvironment and immunotherapy

Methionine metabolism and RNA modifications

Zhang et al. Journal of Hematology & Oncology (2026) 19:3 [https://doi.org/10.1186/s13045-025-01762-7](https://doi.org/10.1186/s13045-025-01762-7) Journal of Hematology & Oncology REVIEW Open Access Mitochondria at the intersections of RNA modifications and metabolism reprogramming implications in cell death, tumor microenvironment, and immunotherapy Jiaxun Zhang1†, Haoxuan Zhang1†, Leifeng Chen2,3, Yuze Wu3, Jiaming Xie1, YannanYang4, Aaron Chen5, Akezhouli Shahatiaili1, Shan Muhammad1, Wenhui Yang6*, Yingli Sun7* andYibo Gao7,8,9* Abstract Mitochondria, the powerhouse of the cell, orchestrate a plethora of critical functions, including energy production, metabolic regulation, programmed cell death, and signal transduction. Their pivotal role in the pathogenesis of numerous diseases underscores their significance. Among the various regulatory mechanisms, RNA modifications emerge as a dominant posttranscriptional modulator of gene expression, increasingly recognized for their profound impact on mitochondrial functions. Groundbreaking discoveries have unveiled compelling links between RNA modifications and oxidative phosphorylation, regulated cell death—particularly cuproptosis—and antitumor immunity, underscoring RNA modifications’ vital role and untapped potential in mitochondrial biology, cancersand aging-related diseases. In this Review, we comprehensively catalog the primary RNA modifications modifiers and their small-molecule inhibitors that influence mitochondrial functions. We explore the latest research delineating RNA modifications’ involvement in mitochondria-related glucose metabolism, regulated cell death, and mitochondrial dynamics, presenting an intricate regulatory network. Furthermore, we investigate the intriguing intersection of RNA modifications and mitochondria-related antitumor immunity, highlighting prospective therapeutic targets to enhance immunotherapy outcomes. This review not only accentuates the critical importance of RNA modifications in mitochondrial function but also paves the way for novel therapeutic strategies in disease treatment. Keywords RNA modifications, Mitochondria, Glucose metabolism, Regulated cell death, Mitochondrial dynamics, Cancer, Tumor microenvironment, Drug resistance, Aging-related disease †Jiaxun Zhang and Haoxuan Zhang contributed equally to this work. *Correspondence: Wenhui Yang [yangwenhui-10012@sxmu.edu.cn](yangwenhui-10012@sxmu.edu.cn)[ ](yangwenhui-10012@sxmu.edu.cn)Yingli Sun [scaroll99@hotmail.com](scaroll99@hotmail.com)[ ](scaroll99@hotmail.com)Yibo Gao [gaoyibo@cicams.ac.cn](gaoyibo@cicams.ac.cn) Full list of author information is available at the end of the article © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, 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 changes were made. 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://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/.)[.](http://creativecommons.org/licenses/by/4.0/.) Zhang et al. Journal of Hematology & Oncology (2026) 19:3 Background Mitochondria function as versatile centers that are crucial for energy production, redox balance, biosynthetic capacity, cellular metabolism, programmed cell death, signal transduction, and intercellular organelle communication [1–3]. Glucose uptake and

FAQs

What are the major cellular roles of mitochondria highlighted in the document?

Mitochondria are described as coordinators of energy production, redox balance, biosynthetic capacity, cellular metabolism, programmed cell death, signal transduction, and intercellular organelle communication.

How do RNA modifications relate to mitochondrial functions according to the review?

RNA modifications are presented as dominant posttranscriptional modulators that influence mitochondrial functions, including oxidative phosphorylation and regulated cell death, and thereby affect antitumor immunity.

Which disease-related intersections does the review emphasize for RNA modifications and mitochondria?

The review emphasizes intersections with cell death pathways, the tumor microenvironment, and immunotherapy, including implications for therapeutic targeting and improved immunotherapy outcomes.

Sep 30, 2026

Uploaded by Terk