ArticleCancer research2019
MFF Regulation of Mitochondrial Cell Death Is a Therapeutic Target in Cancer.
Article in Cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 62 citations in OpenAlex.
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- Mitochondrial proteins as biomarkers of cellular senescence and age-associated diseases.Aging · 2025Review
- Bridging the gap: how patient-derived lung cancer organoids are transforming personalized medicine.Frontiers in cell and developmental biology · 2025Review
- Regulation of mitochondrial dynamics in cardiomyocytes: implications for cardiac health and disease.Frontiers in cell and developmental biology · 2025Review
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- The role of mitochondria in tumor metastasis and advances in mitochondria-targeted cancer therapy.Cancer metastasis reviews · 2024Review
- Mitochondrial elongation impairs breast cancer metastasis.Science advances · 2024Article
- Targeting DNM1L/DRP1-FIS1 axis inhibits high-grade glioma progression by impeding mitochondrial respiratory cristae remodeling.Journal of experimental & clinical cancer research : CR · 2024Article
- Analysis of methylation-driven genes for predicting the prognosis of patients with oral squamous cell carcinoma.Translational cancer research · 2024Article
- Tenovin 3 induces apoptosis and ferroptosis in EGFR 19del non small cell lung cancer cells.Scientific reports · 2024Article
- The Mitochondrial Connection: The Nek Kinases' New Functional Axis in Mitochondrial Homeostasis.Cells · 2024Review
- Mitochondrial dysfunction at the crossroad of cardiovascular diseases and cancer.Journal of translational medicine · 2023Review
- Hypoxia-induced GPCPD1 depalmitoylation triggers mitophagy via regulating PRKN-mediated ubiquitination of VDAC1.Autophagy · 2023Article
- The application of patient-derived organoid in the research of lung cancer.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- Non-Coding RNA-Dependent Regulation of Mitochondrial Dynamics in Cancer Pathophysiology.Non-coding RNA · 2023Review
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24 authors at 5 institutions in 4 countries.
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Abstract
The regulators of mitochondrial cell death in cancer have remained elusive, hampering the development of new therapies. Here, we showed that protein isoforms of mitochondrial fission factor (MFF1 and MFF2), a molecule that controls mitochondrial size and shape, that is, mitochondrial dynamics, were overexpressed in patients with non-small cell lung cancer and formed homo- and heterodimeric complexes with the voltage-dependent anion channel-1 (VDAC1), a key regulator of mitochondrial outer membrane permeability. MFF inserted into the interior hole of the VDAC1 ring using Arg225, Arg236, and Gln241 as key contact sites. A cell-permeable MFF Ser223-Leu243 d-enantiomeric peptidomimetic disrupted the MFF-VDAC1 complex, acutely depolarized mitochondria, and triggered cell death in heterogeneous tumor types, including drug-resistant melanoma, but had no effect on normal cells. In preclinical models, treatment with the MFF peptidomimetic was well-tolerated and demonstrated anticancer activity in patient-derived xenografts, primary breast and lung adenocarcinoma 3D organoids, and glioblastoma neurospheres. These data identify the MFF-VDAC1 complex as a novel regulator of mitochondrial cell death and an actionable therapeutic target in cancer. SIGNIFICANCE: These findings describe mitochondrial fission regulation using a peptidomimetic agent that disturbs the MFF-VDAC complex and displays anticancer activity in multiple tumor models.
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