Oxidative metabolism dysfunction and morphological damage in breast cancer cell mitochondria

22200 Background: Mitochondria are cell energy and signalling source, generating ATP and regulating apoptosis. Altered mitochondrial functions have been identified as causative or contributing factors in many diseases and mitochondriopathy has been recently rekindled as new cancer theory. We report on reduced expression levels of the oxidative phosphorylation system (OXPHOS), structural damage and membrane abnormality of breast-infiltrating ductal carcinoma (IDC) mitochondria. Methods: Mitochondria isolated from HMC-1 (human mammary carcinoma) and HMEC (human mammary epithelial cell) cultures were assayed for OXPHOS expression levels, using Western blot and quantitative densitometry; cryo-immunoelectron microscopy (CIEM) quantitative labelling was performed on unfractionated HMC and HEMC cells and compared to MitoTracker Red and fluorescence immunolabelling merging. Convolution degeneration and ultrastructural abnormalities of mitochondria phenotype were quantitatively established by transmission electron microscopy (TEM). MitoTracker Red and Green co-staining was exploited to assess mitochondria membrane defects. Results: Depressed expression levels were detected for all HMC OXPHOS complexes by both densitometry and CIEM. Drastic reduction was observed for the succinate-dehydrogenase complex II SDH-B protein, while decreasing was reported for the NADH-ubiquinone oxidoreductase complex I NDUFS3 and the ubiquinol cytochrome c reductase complex III UQCRC2 subunits. A significant dropping was detected for the ATP-synthase complex V F1β protein. For the cytochrome-oxidase complex IV (CO) near-depletion of the mitochondrial-encoded COI and no apparent variation of the COIV subunits were observed. Fluorescence immunolabelling overlapped quantitative data. TEM assessed morphology deterioration of HMC cell mitochondria. MitoTracker's co-staining showed modification of mitochondria inner membrane potential and permeability. Conclusions: The relevance of mitochondrial pathobiology in breast cancer therapy has not been adequately explored or clinically exploited. Insights on bioenergetic dysfunction and phenotypic injury of IDC cell mitochondria might thereby provide new cancer hallmarks in breast cancer onset and progression. No significant financial relationships to disclose.