ArticleOncogene2013
PGC-1β mediates adaptive chemoresistance associated with mitochondrial DNA mutations.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- Inhibition of PGC1β-dependent mitochondrial biogenesis enhances EGFR-targeted therapy in lung cancer.EMBO molecular medicine · 2026Article
- Revealing the landscape of targeting mitochondrial functions and behaviors to overcome cancer chemoresistance.Journal of the National Cancer Center · 2025Review
- Respiratory Complex I dysfunction in cancer: from a maze of cellular adaptive responses to potential therapeutic strategies.The FEBS journal · 2022Review
- Extracellular Vesicles and Resistance to Anticancer Drugs: A Tumor Skeleton Key for Unhinging Chemotherapies.Frontiers in oncology · 2022Review
- Review
- Metabolic Plasticity in Chemotherapy Resistance.Frontiers in oncology · 2020Review
- Review
- The PGC-1/ERR network and its role in precision oncology.NPJ precision oncology · 2019Review
- TheGenes · 2018Review
- Mitochondrial Heterogeneity.Frontiers in genetics · 2018Review
- The molecular mechanisms of chemoresistance in cancers.Oncotarget · 2017Review
- Platelet microparticles infiltrating solid tumors transfer miRNAs that suppress tumor growth.Blood · 2017Article
- PGC-1 Coactivators: Shepherding the Mitochondrial Biogenesis of Tumors.Trends in cancer · 2016Review
- Mitochondrial Transcription Factor A and Mitochondrial Genome as Molecular Targets for Cisplatin-Based Cancer Chemotherapy.International journal of molecular sciences · 2015Review
- Hitting the Bull's-Eye in Metastatic Cancers-NSAIDs Elevate ROS in Mitochondria, Inducing Malignant Cell Death.Pharmaceuticals (Basel, Switzerland) · 2015Review
- Mitochondria-Associated Endoplasmic Reticulum Membranes Microenvironment: Targeting Autophagic and Apoptotic Pathways in Cancer Therapy.Frontiers in oncology · 2015Review
- Kaposi's sarcoma herpesvirus microRNAs induce metabolic transformation of infected cells.PLoS pathogens · 2014Article
- Systems biology of cisplatin resistance: past, present and future.Cell death & disease · 2014Review
- The protein disulfide isomerases PDIA4 and PDIA6 mediate resistance to cisplatin-induced cell death in lung adenocarcinoma.Cell death and differentiation · 2014Article
- The emergence of the mitochondrial genome as a partial regulator of nuclear function is providing new insights into the genetic mechanisms underlying age-related complex disease.Human genetics · 2014Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 4 countries.
Funding
Abstract
Primary mitochondrial dysfunction commonly leads to failure in cellular adaptation to stress. Paradoxically, however, nonsynonymous mutations of mitochondrial DNA (mtDNA) are frequently found in cancer cells and may have a causal role in the development of resistance to genotoxic stress induced by common chemotherapeutic agents, such as cis-diammine-dichloroplatinum(II) (cisplatin, CDDP). Little is known about how these mutations arise and the associated mechanisms leading to chemoresistance. Here, we show that the development of adaptive chemoresistance in the A549 non-small-cell lung cancer cell line to CDDP is associated with the hetero- to homoplasmic shift of a nonsynonymous mutation in MT-ND2, encoding the mitochondrial Complex-I subunit ND2. The mutation resulted in a 50% reduction of the NADH:ubiquinone oxidoreductase activity of the complex, which was compensated by increased biogenesis of respiratory chain complexes. The compensatory mitochondrial biogenesis was most likely mediated by the nuclear co-activators peroxisome proliferator-activated receptor gamma co-activator-1α (PGC-1α) and PGC-1β, both of which were significantly upregulated in the CDDP-resistant cells. Importantly, both transient and stable silencing of PGC-1β re-established the sensitivity of these cells to CDDP-induced apoptosis. Remarkably, the PGC-1β-mediated CDDP resistance was independent of the mitochondrial effects of the co-activator. Altogether, our results suggest that partial respiratory chain defects because of mtDNA mutations can lead to compensatory upregulation of nuclear transcriptional co-regulators, in turn mediating resistance to genotoxic stress.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.