Human Ovarian Cancer Tissue Exhibits Increase of Mitochondrial Biogenesis and Cristae Remodeling
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....
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MDPI AG
2019-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/9/1350 |
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| author | Anna Signorile Domenico De Rasmo Antonella Cormio Clara Musicco Roberta Rossi Francesco Fortarezza Luigi Leonardo Palese Vera Loizzi Leonardo Resta Giovanni Scillitani Ettore Cicinelli Francesca Simonetti Anna Ferretta Silvia Russo Antonio Tufaro Gennaro Cormio |
| author_facet | Anna Signorile Domenico De Rasmo Antonella Cormio Clara Musicco Roberta Rossi Francesco Fortarezza Luigi Leonardo Palese Vera Loizzi Leonardo Resta Giovanni Scillitani Ettore Cicinelli Francesca Simonetti Anna Ferretta Silvia Russo Antonio Tufaro Gennaro Cormio |
| author_sort | Anna Signorile |
| collection | DOAJ |
| description | 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 <i>t</i>-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. |
| first_indexed | 2024-03-12T20:18:09Z |
| format | Article |
| id | doaj.art-0e4b15e8564d4f46a4e813eb55630d2a |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T20:18:09Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-0e4b15e8564d4f46a4e813eb55630d2a2023-08-02T01:09:42ZengMDPI AGCancers2072-66942019-09-01119135010.3390/cancers11091350cancers11091350Human Ovarian Cancer Tissue Exhibits Increase of Mitochondrial Biogenesis and Cristae RemodelingAnna Signorile0Domenico De Rasmo1Antonella Cormio2Clara Musicco3Roberta Rossi4Francesco Fortarezza5Luigi Leonardo Palese6Vera Loizzi7Leonardo Resta8Giovanni Scillitani9Ettore Cicinelli10Francesca Simonetti11Anna Ferretta12Silvia Russo13Antonio Tufaro14Gennaro Cormio15Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari “Aldo Moro”, 70124 Bari, ItalyCNR-Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, 70126 Bari, ItalyDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari “Aldo Moro” 70125 Bari, ItalyCNR-Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, 70126 Bari, ItalyDepartment of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, 70124 Bari, ItalyDepartment of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, 70124 Bari, ItalyDepartment of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari “Aldo Moro”, 70124 Bari, ItalyDepartment of Biomedical Sciences and Medical Oncology, University of Bari “Aldo Moro”, 70124 Bari, ItalyDepartment of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, 70124 Bari, ItalyDepartment of Biology, University of Bari “Aldo Moro”, 70125 Bari, ItalyDepartment of Biomedical Sciences and Medical Oncology, University of Bari “Aldo Moro”, 70124 Bari, ItalyDepartment of Biomedical Sciences and Medical Oncology, University of Bari “Aldo Moro”, 70124 Bari, ItalyCNR-Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, 70126 Bari, ItalyDepartment of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari “Aldo Moro”, 70124 Bari, ItalyIstituzional Biobank, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori “Giovanni Paolo II” di Bari, Bari 70124, ItalyDepartment of Biomedical Sciences and Medical Oncology, University of Bari “Aldo Moro”, 70124 Bari, ItalyOvarian 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 <i>t</i>-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.https://www.mdpi.com/2072-6694/11/9/1350ovarian cancermitochondriacAMPmitochondrial biogenesisoxidative phosphorylation system (OXPHOS)SIRT3OPA1prohibitins |
| spellingShingle | Anna Signorile Domenico De Rasmo Antonella Cormio Clara Musicco Roberta Rossi Francesco Fortarezza Luigi Leonardo Palese Vera Loizzi Leonardo Resta Giovanni Scillitani Ettore Cicinelli Francesca Simonetti Anna Ferretta Silvia Russo Antonio Tufaro Gennaro Cormio Human Ovarian Cancer Tissue Exhibits Increase of Mitochondrial Biogenesis and Cristae Remodeling Cancers ovarian cancer mitochondria cAMP mitochondrial biogenesis oxidative phosphorylation system (OXPHOS) SIRT3 OPA1 prohibitins |
| title | Human Ovarian Cancer Tissue Exhibits Increase of Mitochondrial Biogenesis and Cristae Remodeling |
| title_full | Human Ovarian Cancer Tissue Exhibits Increase of Mitochondrial Biogenesis and Cristae Remodeling |
| title_fullStr | Human Ovarian Cancer Tissue Exhibits Increase of Mitochondrial Biogenesis and Cristae Remodeling |
| title_full_unstemmed | Human Ovarian Cancer Tissue Exhibits Increase of Mitochondrial Biogenesis and Cristae Remodeling |
| title_short | Human Ovarian Cancer Tissue Exhibits Increase of Mitochondrial Biogenesis and Cristae Remodeling |
| title_sort | human ovarian cancer tissue exhibits increase of mitochondrial biogenesis and cristae remodeling |
| topic | ovarian cancer mitochondria cAMP mitochondrial biogenesis oxidative phosphorylation system (OXPHOS) SIRT3 OPA1 prohibitins |
| url | https://www.mdpi.com/2072-6694/11/9/1350 |
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