ArticleThe Journal of clinical investigation2013
Mitochondrial complex I activity and NAD+/NADH balance regulate breast cancer progression.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 246 papers.
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Who cites it
246 citing papers in PubMed, 422 citations in OpenAlex.
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- Discovery and preclinical validation of a translationally optimized mitochondrial complex I modulator for Alzheimer's disease.npj drug discovery · 2026Article
- Systems-Level Multi-Omics Analysis Resolves the Mechanism of Action of a Novel Multifunctional Nanosystem Against Triple-Negative Breast Cancer.Pharmaceutics · 2026Article
- Impact of mitochondrial reductive stress due to respiratory chain limitation on cancer via posttranslational modifications.Redox biology · 2026Review
- First Total-Body Kinetics Study ofJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026Article
- Revision of Energy Metabolism Adaptations in High-Level Athletes: From Physical Performance Enhancement to Potential Therapeutic Targets in Mental Disorders.Current issues in molecular biology · 2026Review
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- Optical Redox Imaging of Breast Cancer NADH Redox Status Associated with PGC1α Gene Expression.Academic radiology · 2026Article
- Advances in mitophagy research in hepatocellular carcinoma: mechanisms and therapeutic implications.Journal of gastrointestinal oncology · 2026Review
- Interdependent roles of BRCA1, CtBP, estrogen, and NADH/NAD+ ratio in error-prone repair, breast cancer initiation, and metastasis.Molecular biology reports · 2026Review
- Mitochondria at the heart of aging: structure, function, and failure.Journal of translational medicine · 2026Review
- Multi-tissue analysis identifies mitochondrial genes in chicken aging-induced productivity decline.Journal of animal science and biotechnology · 2026Article
- Discovery and Preclinical Validation of a Clinically Optimized Mitochondrial Complex I Modulator for Alzheimer's Disease.bioRxiv : the preprint server for biology · 2026Article
- Cytochrome c as a central regulator of mitochondrial function in cancer metabolism.Discover oncology · 2026Review
- The hidden players: LncRNA-Encoded micropeptides in cancer hallmarks.Cellular and molecular life sciences : CMLS · 2026Review
- Targeting one-carbon metabolic vulnerabilities of metastasis with therapeutic potential.bioRxiv : the preprint server for biology · 2026Article
- Machine learning framework for mRNA alternative splicing analysis identifies a signature of progression in colorectal adenocarcinoma.Scientific reports · 2026Article
- Navigating the Metabolic-Genomic Paradigm: Mitochondrial Reprogramming as a Driver of Cancer Plasticity.Oncology research · 2026Review
186 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Despite advances in clinical therapy, metastasis remains the leading cause of death in breast cancer patients. Mutations in mitochondrial DNA, including those affecting complex I and oxidative phosphorylation, are found in breast tumors and could facilitate metastasis. This study identifies mitochondrial complex I as critical for defining an aggressive phenotype in breast cancer cells. Specific enhancement of mitochondrial complex I activity inhibited tumor growth and metastasis through regulation of the tumor cell NAD+/NADH redox balance, mTORC1 activity, and autophagy. Conversely, nonlethal reduction of NAD+ levels by interfering with nicotinamide phosphoribosyltransferase expression rendered tumor cells more aggressive and increased metastasis. The results translate into a new therapeutic strategy: enhancement of the NAD+/NADH balance through treatment with NAD+ precursors inhibited metastasis in xenograft models, increased animal survival, and strongly interfered with oncogene-driven breast cancer progression in the MMTV-PyMT mouse model. Thus, aberration in mitochondrial complex I NADH dehydrogenase activity can profoundly enhance the aggressiveness of human breast cancer cells, while therapeutic normalization of the NAD+/NADH balance can inhibit metastasis and prevent disease progression.
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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.