Alteration of expression levels of the oxidative phosphorylation system (OXPHOS) in breast cancer cell mitochondria

Lorenza Putignani, Salvatore Raffa, Roberta Pescosolido, Laura Aimati, Fabrizio Signore, Maria Rosaria Torrisi, Paola Grammatico

Research output: Contribution to journalArticlepeer-review

Abstract

Mitochondria are dynamic intracellular organelles playing a central role in cell metabolism by generating ATP, through the oxidative phosphorylation system (OXPHOS). Altered mitochondrial functions have been identified as causative or contributing factors in some degenerative diseases and are becoming crucial to understanding cancer mechanisms. We report on distinct expression differences between mitochondria of normal and breast-infiltrating ductal carcinoma (IDC) cells. Mitochondria isolated from HMC (human mammary carcinoma) and HMEC (human mammary epithelial cell) cultures were assayed for expression levels of the multi-protein OXPHOS complexes using Western blot and densitometric analyses. Depressed expression levels were detected for all HMC OXPHOS complexes. Drastic signal reduction was observed for the succinate-dehydrogenase complex II iron-sulphur protein SDH-B (3.38%), while decreasing was reported for the NADH-ubiquinone oxidoreductase complex I Fe-S protein 3 NDUFS3 (32.78%) and the ubiquinol-cytochrome c reductase complex III protein 2 UQCRC2 (50.34%). A significant signal dropping was detected for the ATP-synthase complex V F 1β subunit (18.07%). For the cytochrome-oxidase complex IV (CO), near-depletion of the mitochondrial-encoded COI (4.37%) and no apparent variation of the COIV (97.26%) subunits were observed. CO and ATP-synthase were also assayed by cryo-immunoelectron microscopy (CIEM) on unfractionated HMC and HEMC cell mitochondria. COI and F1β differential expression, invariance of COIV levels were corroborated, while HMC mitochondria morphology deterioration was highlighted. MitoTracker Red and fluorescence immunolabelling merging confirmed CIEM data. MitoTracker Red and Green co-staining showed mitochondria membrane property modulation. These data describe bioenergetic and phenotypic alterations of IDC cell mitochondria, possibly providing new cancer hallmarks.

Original languageEnglish
Pages (from-to)439-452
Number of pages14
JournalBreast Cancer Research and Treatment
Volume110
Issue number3
DOIs
Publication statusPublished - Aug 2008

Keywords

  • Breast-infiltrating ductal carcinoma
  • Densitometric analysis of protein expression
  • Mitochondrial fractions
  • Mitochondrial injury
  • Oxidative phosphorylation system (OXPHOS)
  • Warburg's hypothesis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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