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.

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

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
2022

Abstract

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.
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
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/885634
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