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


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
16 05 2022
Historique:
received: 10 12 2021
accepted: 07 04 2022
entrez: 16 5 2022
pubmed: 17 5 2022
medline: 20 5 2022
Statut: epublish

Résumé

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.

Identifiants

pubmed: 35577908
doi: 10.1038/s41598-022-11620-y
pii: 10.1038/s41598-022-11620-y
pmc: PMC9110394
doi:

Substances chimiques

Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha 0
Electron Transport Complex I EC 7.1.1.2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

8020

Subventions

Organisme : Marie Curie
ID : GA 722605
Pays : United Kingdom

Informations de copyright

© 2022. The Author(s).

Références

FEBS J. 2021 Oct 4;:
pubmed: 34606156
Clin Cancer Res. 2018 Jun 1;24(11):2482-2490
pubmed: 29420223
Cancer Res. 2011 Oct 1;71(19):6220-9
pubmed: 21852384
MedComm (2020). 2020 Jul 15;1(2):129-139
pubmed: 34766113
Medchemcomm. 2017 Feb 20;8(3):657-661
pubmed: 30108783
PLoS One. 2013 Jul 09;8(7):e67810
pubmed: 23874451
Cell Rep. 2021 Apr 20;35(3):109002
pubmed: 33882309
Clin Cancer Res. 2015 Jun 15;21(12):2870-9
pubmed: 25779952
Nature. 2008 Feb 21;451(7181):1008-12
pubmed: 18288196
Cancer Treat Rev. 2020 Jun;86:102017
pubmed: 32335505
Trends Endocrinol Metab. 2008 Oct;19(8):269-76
pubmed: 18778951
J Cancer Res Clin Oncol. 2021 Sep;147(9):2555-2567
pubmed: 34089362
Nat Commun. 2019 Feb 22;10(1):903
pubmed: 30796225
Am J Cancer Res. 2019 Feb 01;9(2):198-211
pubmed: 30906622
Cell Metab. 2019 Jan 8;29(1):156-173.e10
pubmed: 30244973
Int J Mol Sci. 2018 Nov 02;19(11):
pubmed: 30400212
Mol Cancer Ther. 2016 May;15(5):774-82
pubmed: 27197257
JCI Insight. 2020 Jun 4;5(11):
pubmed: 32369446
Sci Rep. 2017 Nov 30;7(1):16661
pubmed: 29192176
Methods Mol Biol. 2000;132:365-86
pubmed: 10547847
J Steroid Biochem Mol Biol. 2009 Mar;114(1-2):106-12
pubmed: 19429439
Int J Biochem Cell Biol. 2015 Jun;63:41-5
pubmed: 25668477
Nat Med. 2011 Oct 30;17(11):1498-503
pubmed: 22037646
Cancer Cell. 2019 Jul 8;36(1):84-99.e8
pubmed: 31287994
Cell. 1999 Jul 9;98(1):115-24
pubmed: 10412986
Front Oncol. 2018 Mar 23;8:75
pubmed: 29629336
BMC Bioinformatics. 2006 Feb 22;7:85
pubmed: 16504059
Cell Rep. 2015 Jul 7;12(1):116-127
pubmed: 26119730
Nucleic Acids Res. 2003 Jul 1;31(13):3406-15
pubmed: 12824337
EBioMedicine. 2020 Sep;59:102943
pubmed: 32818805
Hum Mol Genet. 2007 Apr 15;16(8):993-1005
pubmed: 17341490
J Physiol. 2021 Mar;599(6):1745-1757
pubmed: 33347611
Cancer Res. 2020 Apr 15;80(8):1748-1761
pubmed: 32054768
Hum Mol Genet. 2013 Jun 1;22(11):2141-51
pubmed: 23418307
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12017-22
pubmed: 17609368
Nat Med. 2018 Jul;24(7):1036-1046
pubmed: 29892070
Am J Pathol. 2010 Sep;177(3):1053-64
pubmed: 20651229
Oncogene. 2019 Apr;38(16):2885-2898
pubmed: 30568223
Nat Methods. 2012 Jul;9(7):671-5
pubmed: 22930834
Nat Cell Biol. 2014 Oct;16(10):992-1003, 1-15
pubmed: 25241037

Auteurs

Monica De Luise (M)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138, Bologna, Italy.
Center for Applied Biomedical Research, University of Bologna, 40138, Bologna, Italy.
Centro Studi E Ricerca Sulle Neoplasie Ginecologiche (CSR), University of Bologna, 40138, Bologna, Italy.

Manuela Sollazzo (M)

Center for Applied Biomedical Research, University of Bologna, 40138, Bologna, Italy.
Centro Studi E Ricerca Sulle Neoplasie Ginecologiche (CSR), University of Bologna, 40138, Bologna, Italy.
Department of Pharmacy and Biotechnology (FABIT), University of Bologna, 40126, Bologna, Italy.

Eleonora Lama (E)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138, Bologna, Italy.
Center for Applied Biomedical Research, University of Bologna, 40138, Bologna, Italy.
Centro Studi E Ricerca Sulle Neoplasie Ginecologiche (CSR), University of Bologna, 40138, Bologna, Italy.

Camelia Alexandra Coadă (CA)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138, Bologna, Italy.
Center for Applied Biomedical Research, University of Bologna, 40138, Bologna, Italy.
Centro Studi E Ricerca Sulle Neoplasie Ginecologiche (CSR), University of Bologna, 40138, Bologna, Italy.

Licia Bressi (L)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138, Bologna, Italy.
Center for Applied Biomedical Research, University of Bologna, 40138, Bologna, Italy.
Centro Studi E Ricerca Sulle Neoplasie Ginecologiche (CSR), University of Bologna, 40138, Bologna, Italy.

Maria Iorio (M)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138, Bologna, Italy.
Center for Applied Biomedical Research, University of Bologna, 40138, Bologna, Italy.
Centro Studi E Ricerca Sulle Neoplasie Ginecologiche (CSR), University of Bologna, 40138, Bologna, Italy.

Beatrice Cavina (B)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138, Bologna, Italy.
Center for Applied Biomedical Research, University of Bologna, 40138, Bologna, Italy.
Centro Studi E Ricerca Sulle Neoplasie Ginecologiche (CSR), University of Bologna, 40138, Bologna, Italy.

Luigi D'Angelo (L)

Center for Applied Biomedical Research, University of Bologna, 40138, Bologna, Italy.
Centro Studi E Ricerca Sulle Neoplasie Ginecologiche (CSR), University of Bologna, 40138, Bologna, Italy.
Department of Pharmacy and Biotechnology (FABIT), University of Bologna, 40126, Bologna, Italy.

Sara Milioni (S)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138, Bologna, Italy.
Center for Applied Biomedical Research, University of Bologna, 40138, Bologna, Italy.
Centro Studi E Ricerca Sulle Neoplasie Ginecologiche (CSR), University of Bologna, 40138, Bologna, Italy.

Lorena Marchio (L)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138, Bologna, Italy.
Center for Applied Biomedical Research, University of Bologna, 40138, Bologna, Italy.
Centro Studi E Ricerca Sulle Neoplasie Ginecologiche (CSR), University of Bologna, 40138, Bologna, Italy.

Stefano Miglietta (S)

Center for Applied Biomedical Research, University of Bologna, 40138, Bologna, Italy.
Centro Studi E Ricerca Sulle Neoplasie Ginecologiche (CSR), University of Bologna, 40138, Bologna, Italy.
Department of Pharmacy and Biotechnology (FABIT), University of Bologna, 40126, Bologna, Italy.

Sara Coluccelli (S)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138, Bologna, Italy.
Center for Applied Biomedical Research, University of Bologna, 40138, Bologna, Italy.
Centro Studi E Ricerca Sulle Neoplasie Ginecologiche (CSR), University of Bologna, 40138, Bologna, Italy.

Greta Tedesco (G)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138, Bologna, Italy.
Center for Applied Biomedical Research, University of Bologna, 40138, Bologna, Italy.
Centro Studi E Ricerca Sulle Neoplasie Ginecologiche (CSR), University of Bologna, 40138, Bologna, Italy.

Anna Ghelli (A)

Center for Applied Biomedical Research, University of Bologna, 40138, Bologna, Italy.
Centro Studi E Ricerca Sulle Neoplasie Ginecologiche (CSR), University of Bologna, 40138, Bologna, Italy.
Department of Pharmacy and Biotechnology (FABIT), University of Bologna, 40126, Bologna, Italy.

Silvia Lemma (S)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138, Bologna, Italy.
Center for Applied Biomedical Research, University of Bologna, 40138, Bologna, Italy.
Centro Studi E Ricerca Sulle Neoplasie Ginecologiche (CSR), University of Bologna, 40138, Bologna, Italy.

Anna Myriam Perrone (AM)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138, Bologna, Italy.
Division of Oncologic Gynecology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138, Bologna, Italy.

Ivana Kurelac (I)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138, Bologna, Italy. ivana.kurelac@unibo.it.
Center for Applied Biomedical Research, University of Bologna, 40138, Bologna, Italy. ivana.kurelac@unibo.it.
Centro Studi E Ricerca Sulle Neoplasie Ginecologiche (CSR), University of Bologna, 40138, Bologna, Italy. ivana.kurelac@unibo.it.

Luisa Iommarini (L)

Center for Applied Biomedical Research, University of Bologna, 40138, Bologna, Italy. luisa.iommarini2@unibo.it.
Centro Studi E Ricerca Sulle Neoplasie Ginecologiche (CSR), University of Bologna, 40138, Bologna, Italy. luisa.iommarini2@unibo.it.
Department of Pharmacy and Biotechnology (FABIT), University of Bologna, 40126, Bologna, Italy. luisa.iommarini2@unibo.it.

Anna Maria Porcelli (AM)

Center for Applied Biomedical Research, University of Bologna, 40138, Bologna, Italy.
Centro Studi E Ricerca Sulle Neoplasie Ginecologiche (CSR), University of Bologna, 40138, Bologna, Italy.
Department of Pharmacy and Biotechnology (FABIT), University of Bologna, 40126, Bologna, Italy.
Interdepartmental Center of Industrial Research (CIRI) Life Science and Health Technologies, University of Bologna, 40064, Ozzano dell'Emilia, Italy.

Giuseppe Gasparre (G)

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138, Bologna, Italy. giuseppe.gasparre3@unibo.it.
Center for Applied Biomedical Research, University of Bologna, 40138, Bologna, Italy. giuseppe.gasparre3@unibo.it.
Centro Studi E Ricerca Sulle Neoplasie Ginecologiche (CSR), University of Bologna, 40138, Bologna, Italy. giuseppe.gasparre3@unibo.it.

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Classifications MeSH