ArticleNature communications2015
Mitochondrial uncoupling links lipid catabolism to Akt inhibition and resistance to tumorigenesis.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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
20 citing papers in PubMed, 29 citations in OpenAlex.
- Mitochondria as a Therapeutic Target in Metabolic Disorders.Mini reviews in medicinal chemistry · 2026Review
- Nitazoxanide protects against heart failure with preserved ejection and metabolic syndrome induced by high-fat diet (HFD) plus L-NAME "two-hit" in mice.Acta pharmaceutica Sinica. B · 2025Article
- The clinical antiprotozoal drug nitazoxanide and its metabolite tizoxanide extendActa pharmaceutica Sinica. B · 2024Article
- Article
- Molecular map of chronic lymphocytic leukemia and its impact on outcome.Nature genetics · 2022Article
- Identification of a prognostic signature in colorectal cancer using combinatorial algorithm-driven analysis.The journal of pathology. Clinical research · 2022Article
- Exploring the therapeutic potential of mitochondrial uncouplers in cancer.Molecular metabolism · 2021Review
- Review
- Triclosan induces ROS-dependent cell death and autophagy in A375 melanoma cells.Oncology letters · 2020Article
- 20,000 picometers under the OMM: diving into the vastness of mitochondrial metabolite transport.EMBO reports · 2020Review
- Review
- UCP2 Deficiency Increases Colon Tumorigenesis by Promoting Lipid Synthesis and Depleting NADPH for Antioxidant Defenses.Cell reports · 2019Article
- Targeting lonidamine to mitochondria mitigates lung tumorigenesis and brain metastasis.Nature communications · 2019Article
- Article
- Mitochondrial Uncoupling Proteins: Subtle Regulators of Cellular Redox Signaling.Antioxidants & redox signaling · 2018Review
- Inhibition of mitochondrial UCP1 and UCP3 by purine nucleotides and phosphate.Biochimica et biophysica acta. Biomembranes · 2018Article
- Gelsolin regulates proliferation, apoptosis and invasion in natural killer/T-cell lymphoma cells.Biology open · 2018Article
- Lipid catabolism inhibition sensitizes prostate cancer cells to antiandrogen blockade.Oncotarget · 2017Article
- Oxidative and nitrosative stress during pulmonary ischemia-reperfusion injury: from the lab to the OR.Annals of translational medicine · 2017Review
- Chewing the fat for Akt1 inhibition and oncosuppression.Molecular & cellular oncology · 2016Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
To support growth, tumour cells reprogramme their metabolism to simultaneously upregulate macromolecular biosynthesis while maintaining energy production. Uncoupling proteins (UCPs) oppose this phenotype by inducing futile mitochondrial respiration that is uncoupled from ATP synthesis, resulting in nutrient wasting. Here using a UCP3 transgene targeted to the basal epidermis, we show that forced mitochondrial uncoupling inhibits skin carcinogenesis by blocking Akt activation. Similarly, Akt activation is markedly inhibited in UCP3 overexpressing primary human keratinocytes. Mechanistic studies reveal that uncoupling increases fatty acid oxidation and membrane phospholipid catabolism, and impairs recruitment of Akt to the plasma membrane. Overexpression of Akt overcomes metabolic regulation by UCP3, rescuing carcinogenesis. These findings demonstrate that mitochondrial uncoupling is an effective strategy to limit proliferation and tumorigenesis through inhibition of Akt, and illuminate a novel mechanism of crosstalk between mitochondrial metabolism and growth signalling.
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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.