Regulation of tumor cell mitochondrial Homeostasis by an organelle-specific Hsp90 chaperone network
Cited 165 times inCited 153 times in
- Regulation of tumor cell mitochondrial Homeostasis by an organelle-specific Hsp90 chaperone network
- Kang, Byoung Heon; Plescia, Janet; Dohi, Takehiko; Rosa, Jack; Doxsey, Stephen J.; Altieri, Dario C.
- Issue Date
- CELL PRESS
- CELL, v.131, no.2, pp.257 - 270
- 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, contain Hsp90 and its related molecule, TRAP-1. These chaperones interact with Cyclophilin D, 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.
- Appears in Collections:
- BIO_Journal Papers
- Files in This Item:
- There are no files associated with this item.
can give you direct access to the published full text of this article. (UNISTARs only)
Show full item record
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.