Inducing respiratory complex I impairment elicits an increase in PGC1α in ovarian cancer

Anticancer strategies aimed at inhibiting Complex I of the mitochondrial respiratory chain are increasingly being attempted in solid tumors, as functional oxidative phosphorylation is vital for cancer cells. Using ovarian cancer as a model, we show that a compensatory response to an energy crisis in...

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Published in:Scientific reports 2022-05, Vol.12 (1), p.8020-8020, Article 8020
Main Authors: De Luise, Monica, Sollazzo, Manuela, Lama, Eleonora, Coadă, Camelia Alexandra, Bressi, Licia, Iorio, Maria, Cavina, Beatrice, D’Angelo, Luigi, Milioni, Sara, Marchio, Lorena, Miglietta, Stefano, Coluccelli, Sara, Tedesco, Greta, Ghelli, Anna, Lemma, Silvia, Perrone, Anna Myriam, Kurelac, Ivana, Iommarini, Luisa, Porcelli, Anna Maria, Gasparre, Giuseppe
Format: Article
Language:English
Subjects:
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Carcinoma, Ovarian Epithelial - metabolism
Carcinoma, Ovarian Epithelial - pathology
Electron transport chain
Electron Transport Complex I - antagonists & inhibitors
Electron Transport Complex I - genetics
Electron Transport Complex I - metabolism
Female
Gene expression
Humanities and Social Sciences
Humans
Kinases
Mitochondria
multidisciplinary
Organelle Biogenesis
Ovarian cancer
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Oxidative Phosphorylation
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - genetics
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism
Phosphorylation
Science
Science (multidisciplinary)
Solid tumors
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Summary:Anticancer strategies aimed at inhibiting Complex I of the mitochondrial respiratory chain are increasingly being attempted in solid tumors, as functional oxidative phosphorylation is vital for cancer cells. Using ovarian cancer as a model, we show that a compensatory response to an energy crisis induced by Complex I genetic ablation or pharmacological inhibition is an increase in the mitochondrial biogenesis master regulator PGC1α, a pleiotropic coactivator of transcription regulating diverse biological processes within the cell. We associate this compensatory response to the increase in PGC1α target gene expression, setting the basis for the comprehension of the molecular pathways triggered by Complex I inhibition that may need attention as drawbacks before these approaches are implemented in ovarian cancer care.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-022-11620-y