Regulation of Tumor Cell Mitochondrial Homeostasis by an Organelle-Specific Hsp90 Chaperone Network.
Kang BH, Plescia J, Dohi T, Rosa J, Doxsey SJ, Altieri DC
Cell (2007)
Category: cancer, chaperone, mitochondria-biogenesis ¤ Added: Oct 22, 2007 ¤ Rating: ◊◊
Molecular chaperones, especially members of the heat shock protein 90 (Hsp90) family, are thought to promote tumor cell survival, but this function is not well understood. Here, we show that mitochondria of tumor cells, but not most normal tissues, containHsp90andits relatedmolecule, TRAP-1. These chaperones interact with CyclophilinD, an immunophilin that induces mitochondrial cell death, and antagonize its function via protein folding/refolding mechanisms. Disabling this pathway using novel Hsp90 ATPase antagonists directed to mitochondria causes sudden collapse of mitochondrial function and selective tumor cell death. Therefore, Hsp90- directed chaperones are regulators of mitochondrial integrity, and their organelle-specific antagonists may provide a previously undescribed class of potent anticancer agents.