NAF-1 and mitoNEET are central to human breast cancer proliferation by maintaining mitochondrial homeostasis and promoting tumor growth

Yang Sung Sohn, Sagi Tamir, Luhua Song, Dorit Michaeli, Imad Matouk, Andrea R. Conlan, Yael Harir, Sarah H. Holt, Vladimir Shulaev, Mark L. Paddock, Abraham Hochberg, Ioav Z. Cabanchick, José N. Onuchic, Patricia A. Jennings, Rachel Nechushtai, Ron Mittler

Research output: Contribution to journalArticlepeer-review

Abstract

Mitochondria are emerging as important players in the transformation process of cells, maintaining the biosynthetic and energetic capacities of cancer cells and serving as one of the primary sites of apoptosis and autophagy regulation. Although several avenues of cancer therapy have focused on mitochondria, progress in developing mitochondria-targeting anticancer drugs nonetheless has been slow, owing to the limited number of known mitochondrial target proteins that link metabolism with autophagy or cell death. Recent studies have demonstrated that two members of the newly discovered family of NEET proteins, NAF-1 (CISD2) and mitoNEET (mNT; CISD1), could play such a role in cancer cells. NAF-1 was shown to be a key player in regulating autophagy, and mNT was proposed to mediate iron and reactive oxygen homeostasis in mitochondria. Here we show that the protein levels of NAF-1 and mNT are elevated in human epithelial breast cancer cells, and that suppressing the level of these proteins using shRNA results in significantly reduced cell proliferation and tumor growth, decreased mitochondrial performance, uncontrolled accumulation of iron and reactive oxygen in mitochondria, and activation of autophagy. Our findings highlight NEET proteins as promising mitochondrial targets for cancer therapy.

Original languageAmerican English
Pages (from-to)14676-14681
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number36
DOIs
StatePublished - 3 Sep 2013

Keywords

  • Cisd1
  • Cisd2
  • MCF7
  • MDA-MB-231
  • Miner1

All Science Journal Classification (ASJC) codes

  • General

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