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Article

Human Ovarian Cancer Tissue Exhibits Increase of Mitochondrial Biogenesis and Cristae Remodeling

1
Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari “Aldo Moro”, 70124 Bari, Italy
2
CNR-Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, 70126 Bari, Italy
3
Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari “Aldo Moro” 70125 Bari, Italy
4
Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, 70124 Bari, Italy
5
Department of Biomedical Sciences and Medical Oncology, University of Bari “Aldo Moro”, 70124 Bari, Italy
6
Department of Biology, University of Bari “Aldo Moro”, 70125 Bari, Italy
7
Istituzional Biobank, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori “Giovanni Paolo II” di Bari, Bari 70124, Italy
8
Gynecologic Oncology Unit, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori “Giovanni Paolo II” di Bari, Bari 70124, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2019, 11(9), 1350; https://doi.org/10.3390/cancers11091350
Submission received: 7 August 2019 / Revised: 28 August 2019 / Accepted: 4 September 2019 / Published: 12 September 2019

Abstract

Ovarian cancer (OC) is the most lethal gynecologic cancer characterized by an elevated apoptosis resistance that, potentially, leads to chemo-resistance in the recurrent disease. Mitochondrial oxidative phosphorylation was found altered in OC, and mitochondria were proposed as a target for therapy. Molecular evidence suggests that the deregulation of mitochondrial biogenesis, morphology, dynamics, and apoptosis is involved in carcinogenesis. However, these mitochondrial processes remain to be investigated in OC. Eighteen controls and 16 OC tissues (serous and mucinous) were collected. Enzymatic activities were performed spectrophotometrically, mitochondrial DNA (mtDNA) content was measured by real-time-PCR, protein levels were determined by Western blotting, and mitochondrial number and structure were measured by electron microscopy. Statistical analysis was performed using Student’s t-test, Mann-Whitney U test, and principal component analysis (PCA). We found, in OC, that increased mitochondrial number associated with increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and mitochondrial transcription factor A (TFAM) protein levels, as well as mtDNA content. The OC mitochondria presented an increased maximum length, as well as reduced cristae width and junction diameter, associated with increased optic atrophy 1 protein (OPA1) and prohibitin 2 (PHB2) protein levels. In addition, in OC tissues, augmented cAMP and sirtuin 3 (SIRT3) protein levels were observed. PCA of the 25 analyzed biochemical parameters classified OC patients in a distinct group from controls. We highlight a “mitochondrial signature” in OC that could result from cooperation of the cAMP pathway with the SIRT3, OPA1, and PHB2 proteins.
Keywords: ovarian cancer; mitochondria; cAMP; mitochondrial biogenesis; oxidative phosphorylation system (OXPHOS); SIRT3; OPA1; prohibitins ovarian cancer; mitochondria; cAMP; mitochondrial biogenesis; oxidative phosphorylation system (OXPHOS); SIRT3; OPA1; prohibitins

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MDPI and ACS Style

Signorile, A.; De Rasmo, D.; Cormio, A.; Musicco, C.; Rossi, R.; Fortarezza, F.; Palese, L.L.; Loizzi, V.; Resta, L.; Scillitani, G.; et al. Human Ovarian Cancer Tissue Exhibits Increase of Mitochondrial Biogenesis and Cristae Remodeling. Cancers 2019, 11, 1350. https://doi.org/10.3390/cancers11091350

AMA Style

Signorile A, De Rasmo D, Cormio A, Musicco C, Rossi R, Fortarezza F, Palese LL, Loizzi V, Resta L, Scillitani G, et al. Human Ovarian Cancer Tissue Exhibits Increase of Mitochondrial Biogenesis and Cristae Remodeling. Cancers. 2019; 11(9):1350. https://doi.org/10.3390/cancers11091350

Chicago/Turabian Style

Signorile, Anna, Domenico De Rasmo, Antonella Cormio, Clara Musicco, Roberta Rossi, Francesco Fortarezza, Luigi Leonardo Palese, Vera Loizzi, Leonardo Resta, Giovanni Scillitani, and et al. 2019. "Human Ovarian Cancer Tissue Exhibits Increase of Mitochondrial Biogenesis and Cristae Remodeling" Cancers 11, no. 9: 1350. https://doi.org/10.3390/cancers11091350

APA Style

Signorile, A., De Rasmo, D., Cormio, A., Musicco, C., Rossi, R., Fortarezza, F., Palese, L. L., Loizzi, V., Resta, L., Scillitani, G., Cicinelli, E., Simonetti, F., Ferretta, A., Russo, S., Tufaro, A., & Cormio, G. (2019). Human Ovarian Cancer Tissue Exhibits Increase of Mitochondrial Biogenesis and Cristae Remodeling. Cancers, 11(9), 1350. https://doi.org/10.3390/cancers11091350

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