Conlan, Andrea R.
Holt, Sarah H.
Paddock, Mark L.
Cabanchick, Ioav Z.
Onuchic, José N.
Jennings, Patricia A.
Sohn, Yang-Sung, Tamir, Sagi, Song, Luhua, et al., . "NAF-1 and mitoNEET are central to human breast cancer proliferation by maintaining mitochondrial homeostasis and promoting tumor growth." PNAS Early Edition, (2013) http://dx.doi.org/10.1073/pnas.1313198110.
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.
NAF-1 and mitoNEET are central to human breast cancer proliferation by maintaining mitochondrial homeostasis and promoting tumor growth
Cancer Prevention and Research Institute of Texas
National Institutes of Health
PNAS Early Edition
Center for Theoretical Biological Physics
National Academy of Sciences
GM54038 (National Institutes of Health)
GM101467 (National Institutes of Health)