Probing novel roles of the mitochondrial uniporter in ovarian cancer cells using nanoparticles

Rochelle R. Arvizo, Daniel F. Moyano, Sounik Saha, Michael A. Thompson, Resham Bhattacharya, Vincent M. Rotello, Y. S. Prakash, Priyabrata Mukherjee

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Nanoparticles provide a potent tool for targeting and understanding disease mechanisms. In this regard, cancer cells are surprisingly resistant to the expected toxic effects of positively charged gold nanoparticles ( +AuNPs). Our investigations led to the identification of MICU1, regulator of mitochondrial calcium uniporter, as a key molecule conferring cancer cells with resistance to +AuNPs. The increase in cytosolic [Ca2+]cyto in malignant cells induced by +AuNPs is counteracted by MICU1, preventing cell death. Pharmacological or siRNA-mediated inhibition of mitochondrial Ca+2 entry leads to endoplasmic reticulum stress and sensitizes cancer cells to +AuNP- induced cytotoxicity. Silencing MICU1 decreases Bcl-2 expression and increases caspase-3 activity and cytosolic cytochrome c levels, thus initiating the mitochondrial pathway for apoptosis: effects further enhanced by +AuNPs. This study highlights the potential of nanomaterials as a tool to broaden our understanding of cellular processes, establishes MICU1 as a novel regulator of the machinery in cancer cells that prevents apoptosis, and emphasizes the need to synergize nanoparticle design with understanding of mitochondrial machinery for enhancing targeted cellular toxicity.

Original languageEnglish (US)
Pages (from-to)17610-17618
Number of pages9
JournalJournal of Biological Chemistry
Volume288
Issue number24
DOIs
StatePublished - Jun 14 2013

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Arvizo, R. R., Moyano, D. F., Saha, S., Thompson, M. A., Bhattacharya, R., Rotello, V. M., Prakash, Y. S., & Mukherjee, P. (2013). Probing novel roles of the mitochondrial uniporter in ovarian cancer cells using nanoparticles. Journal of Biological Chemistry, 288(24), 17610-17618. https://doi.org/10.1074/jbc.M112.435206