Increase in proteins involved in mitochondrial fission, mitophagy, proteolysis and antioxidant response in type I endometrial cancer as an adaptive response to respiratory complex I deficiency

Antonella Cormio, Clara Musicco, Giuseppe Gasparre, Gennaro Cormio, Vito Pesce, Anna Maria Sardanelli, Maria Nicola Gadaleta

Research output: Contribution to journalArticlepeer-review

Abstract

Pathogenic mtDNA mutations associated with alterations of respiratory complex I, mitochondrial proliferation (oncocytic-like phenotype) and increase in antioxidant response were previously reported in type I endometrial carcinoma (EC). To evaluate whether in the presence of pathogenic mtDNA mutations other mitochondrial adaptive processes are triggered by cancer cells, the expression level of proteins involved in mitochondrial dynamics, mitophagy, proteolysis and apoptosis were evaluated in type I ECs harboring pathogenic mtDNA mutations and complex I deficiency. An increase in the fission protein Drp1, in the mitophagy protein BNIP3, in the mitochondrial protease CLPP, in the antioxidant and anti-apoptotic protein ALR and in Bcl-2 as well as a decrease in the fusion protein Mfn2 were found in cancer compared to matched non malignant tissue. Moreover, the level of these proteins was measured in type I EC, in hyperplastic (the premalignant form) and in non malignant tissues to verify whether the altered expression of these proteins is a common feature of endometrial cancer and of hyperplastic tissue. This analysis confirmed in type I EC samples, but not in hyperplasia, an alteration of the expression level of these proteins. These results suggest that in this cancer mitochondrial fission, antioxidant and anti-apoptotic response may be activated, as well as the discharge of damaged mitochondrial proteins as adaptation processes to mitochondrial dysfunction.

Original languageEnglish
Pages (from-to)85-90
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume491
Issue number1
DOIs
Publication statusPublished - Sep 9 2017

Keywords

  • ALR
  • BNIP3
  • CLPP
  • Complex I deficiency
  • Endometrial carcinoma
  • Mitochondrial dynamics

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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