Human ovarian cancer tissue exhibits increase of mitochondrial biogenesis and cristae remodeling

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number1350
JournalCancers
Volume11
Issue number9
DOIs
Publication statusPublished - Sep 2019

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Keywords

  • CAMP
  • Mitochondria
  • Mitochondrial biogenesis
  • OPA1
  • Ovarian cancer
  • Oxidative phosphorylation system (OXPHOS)
  • Prohibitins
  • SIRT3

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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