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.