---
title: "Mitochondrial Genome Alterations in Cancer: Mutations, Mitoepigenetics, and Targeted Therapies"
id: "pubmed-42385482"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42385482"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42385482/"
doi: "10.1016/j.bbrc.2026.154218"
published_at: "2026-09-03T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Mitochondrial Genome Alterations in Cancer: Mutations, Mitoepigenetics, and Targeted Therapies
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42385482
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42385482/)
- **DOI:** [10.1016/j.bbrc.2026.154218](https://doi.org/10.1016%2Fj.bbrc.2026.154218)
- **Published At:** 2026-09-03T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Mitochondria are central to cellular energy, metabolism, and apoptosis; their dysfunction is increasingly recognized as a hallmark of cancer. - The mitochondrial genome encodes essential subunits of **OXPHOS**, as well as tRNAs and rRNAs required for mitochondrial function. - **Mitochondrial DNA** (mtDNA) is especially vulnerable because it lacks protective histones and efficient repair mechanisms, increasing susceptibility to mutations and epigenetic changes. - Alterations discussed include microsatellite instability, somatic mtDNA mutations, and epigenetic modifications such as methylation and interactions with non-coding RNAs. - These changes disrupt mitochondrial function, causing defective **OXPHOS**, metabolic reprogramming (including the **Warburg effect**), increased **reactive oxygen species (ROS)** production, and evasion of apoptosis. - MEG (mitochondrial-encoded gene) alterations show tissue-specific and stage-dependent patterns across several cancers, with examples highlighted in breast, colorectal, lung, and ovarian malignancies. - MEG alterations contribute to clinically relevant problems including chemoresistance and tumor metastasis, creating barriers to effective cancer treatment. - The review positions MEGs as potential diagnostic, prognostic, and therapeutic biomarkers for precision oncology. - Emerging therapeutic strategies covered include **mitochondrial gene editing**, **allotopic expression**, and **nanocarrier-based delivery** systems aimed at targeting MEGs. - The article synthesizes current evidence and outlines future directions but does not provide primary clinical trial outcomes or specific quantitative results within the abstract; detailed experimental findings and clinical data were not reported in the abstract.
## Clinical Analysis & Structured Key Points
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Epub 2026 Jun 30. # Mitochondrial genome alterations in cancer: From mutations and epigenetics to targeted therapiesack [Sachin Shetty](https://pubmed.ncbi.nlm.nih.gov/?term=Shetty+S&cauthor_id=42385482)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42385482/#full-view-affiliation-1 "Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India."), [Nisarga M Padmasali](https://pubmed.ncbi.nlm.nih.gov/?term=Padmasali+NM&cauthor_id=42385482)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42385482/#full-view-affiliation-1 "Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India."), [Divya Adiga](https://pubmed.ncbi.nlm.nih.gov/?term=Adiga+D&cauthor_id=42385482)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42385482/#full-view-affiliation-1 "Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India."), [Shama Prasada Kabekkodu](https://pubmed.ncbi.nlm.nih.gov/?term=Kabekkodu+SP&cauthor_id=42385482)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42385482/#full-view-affiliation-2 "Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India. Electronic address: shama.prasada@manipal.edu.") Affiliations Expand ### Affiliations * 1 Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India. * 2 Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India. Electronic address: shama.prasada@manipal.edu. * PMID: **42385482** * DOI: [ 10.1016/j.bbrc.2026.154218 ](https://doi.org/10.1016/j.bbrc.2026.154218) Free article Item in Clipboard Review # Mitochondrial genome alterations in cancer: From mutations and epigenetics to targeted therapiesack Sachin Shetty et al. Biochem Biophys Res Commun. 2026. Free article Show details Display options Display options Format Abstract PubMed PMID Biochem Biophys Res Commun Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Biochem+Biophys+Res+Commun%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Biochem+Biophys+Res+Commun%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42385482/) . 2026 Sep 3:829:154218. doi: 10.1016/j.bbrc.2026.154218. Epub 2026 Jun 30. ### Authors [Sachin Shetty](https://pubmed.ncbi.nlm.nih.gov/?term=Shetty+S&cauthor_id=42385482)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42385482/#short-view-affiliation-1 "Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India."), [Nisarga M Padmasali](https://pubmed.ncbi.nlm.nih.gov/?term=Padmasali+NM&cauthor_id=42385482)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42385482/#short-view-affiliation-1 "Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India."), [Divya Adiga](https://pubmed.ncbi.nlm.nih.gov/?term=Adiga+D&cauthor_id=42385482)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42385482/#short-view-affiliation-1 "Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India."), [Shama Prasada Kabekkodu](https://pubmed.ncbi.nlm.nih.gov/?term=Kabekkodu+SP&cauthor_id=42385482)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42385482/#short-view-affiliation-2 "Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India. Electronic address: shama.prasada@manipal.edu.") ### Affiliations * 1 Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India. * 2 Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India. Electronic address: shama.prasada@manipal.edu. * PMID: **42385482** * DOI: [ 10.1016/j.bbrc.2026.154218 ](https://doi.org/10.1016/j.bbrc.2026.154218) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract Mitochondria play a central role in cellular energetics, metabolism, and apoptosis, and their dysfunction is increasingly recognized as a hallmark of cancer. The mitochondrial genome encodes essential subunits of oxidative phosphorylation (OXPHOS) complexes, tRNAs, and rRNAs, which are critical for mitochondrial functions. However, mitochondrial DNA (mtDNA) lacks protective histones and efficient repair mechanisms, rendering it highly susceptible to mutations and epigenetic changes. This review examines the role of mitochondrial-encoded genes (MEGs) in cancer progression, emphasizing the molecular mechanisms through which alterations in these genes contribute to tumorigenesis. We discuss how microsatellite instability, somatic mutations, and epigenetic modifications, such as methylation and non-coding RNA interactions, disrupt mitochondrial function, leading to defective OXPHOS, metabolic reprogramming (including the Warburg effect), elevated reactive oxygen species (ROS) production, and evasion of apoptosis. Furthermore, we highlight the tissue-specific and stage-dependent alterations in MEGs across various cancers, including breast, colorectal, lung, and ovarian malignancies, and explore their potential as diagnostic, prognostic, and therapeutic biomarkers. Finally, we evaluate emerging therapeutic strategies targeting MEGs, including mitochondrial gene editing, allotopic expression, and nanocarrier-based delivery systems, offering insights into future directions in precision oncology. We also discuss how MEG alterations contribute to the Warburg effect, chemoresistance, and tumor metastasis, which are critical barriers to effective cancer treatment. This synthesis highlights the pivotal role of mitochondrial genetics in cancer biology and positions MEGs as promising targets for innovative anticancer therapies. **Keywords:** Cancer research; Epigenetics; Microsatellite instability; Mitochondrial-encoded genes; OXPHOS; Precision medicine; Targeted cancer therapy; mtDNA mutations. Copyright © 2026 Elsevier Inc. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ## Similar articles * [ Targeting the epigenome and tumor heterogeneity: advances in immunotherapy for chemoresistant metastatic colorectal cancer. ](https://pubmed.ncbi.nlm.nih.gov/41403952/) Cao Y, Beeraka NM, Efetov SK, Liu Z, Otabekov AA, Basappa B, Wang W, Ma D.Cao Y, et al.Front Immunol. 2025 Dec 1;16:1623117. doi: 10.3389/fimmu.2025.1623117. eCollection 2025.Front Immunol. 2025.PMID: 41403952Free PMC article.Review. * [ Mitochondrial mutations and mitoepigenetics: Focus on regulation of oxidative stress-induced responses in breast cancers. ](https://pubmed.ncbi.nlm.nih.gov/33035656/) Chen K, Lu P, Beeraka NM, Sukocheva OA, Madhunapantula SV, Liu J, Sinelnikov MY, Nikolenko VN, Bulygin KV, Mikhaleva LM, Reshetov IV, Gu Y, Zhang J, Cao Y, Somasundaram SG, Kirkland CE, Fan R, Aliev G.Chen K, et al.Semin Cancer Biol. 2022 Aug;83:556-569. doi: 10.1016/j.semcancer.2020.09.012. Epub 2020 Oct 6.Semin Cancer Biol. 2022.PMID: 33035656Review. * [ Mitochondrial DNA mutations and breast tumorigenesis. ](https://pubmed.ncbi.nlm.nih.gov/24140413/) Yadav N, Chandra D.Yadav N, et al.Biochim Biophys Acta. 2013 Dec;1836(2):336-44. doi: 10.1016/j.bbcan.2013.10.002. Epub 2013 Oct 16.Biochim Biophys Acta. 2013.PMID: 24140413Free PMC article.Review. * [ Mitochondria and cancer chemoresistance. ](https://pubmed.ncbi.nlm.nih.gov/28161329/) Guerra F, Arbini AA, Moro L.Guerra F, et al.Biochim Biophys Acta Bioenerg. 2017 Aug;1858(8):686-699. doi: 10.1016/j.bbabio.2017.01.012. Epub 2017 Feb 1.Biochim Biophys Acta Bioenerg. 2017.PMID: 28161329Review. * [ Mitochondrial biogenesis: pharmacological approaches. ](https://pubmed.ncbi.nlm.nih.gov/24606795/) Valero T.Valero T.Curr Pharm Des. 2014;20(35):5507-9. doi: 10.2174/138161282035140911142118.Curr Pharm Des. 2014.PMID: 24606795 [ See all similar articles ](https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed&from_uid=42385482) ## Publication types * Review Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Review%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Review) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42385482/) ## MeSH terms * Animals Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Animals%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Animals) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42385482/) * DNA, Mitochondrial / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22DNA%2C+Mitochondrial%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=DNA%2C+Mitochondrial) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42385482/) * Epigenesis, Genetic* Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Epigenesis%2C+Genetic%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Epigenesis%2C+Genetic) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42385482/) * Genome, Mitochondrial* / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Genome%2C+Mitochondrial%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Genome%2C+Mitochondrial) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42385482/) * Humans Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Humans) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42385482/) * Metabolic Reprogramming Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Metabolic+Reprogramming%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Metabolic+Reprogramming) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42385482/) * Mitochondria / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Mitochondria%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Mitochondria) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42385482/) * Mitochondria / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Mitochondria%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Mitochondria) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42385482/) * Molecular Targeted Therapy Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Molecular+Targeted+Therapy%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Molecular+Targeted+Therapy) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42385482/) * Mutation* Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Mutation%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Mutation) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42385482/) * Neoplasms* / drug therapy Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Neoplasms%2Fdrug+therapy%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Neoplasms) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42385482/) * Neoplasms* / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Neoplasms%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Neoplasms) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42385482/) * Neoplasms* / pathology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Neoplasms%2Fpathology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Neoplasms) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42385482/) * Neoplasms* / therapy Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Neoplasms%2Ftherapy%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Neoplasms) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.
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