Format

Send to

Choose Destination
Cell. 2007 Oct 19;131(2):257-70.

Regulation of tumor cell mitochondrial homeostasis by an organelle-specific Hsp90 chaperone network.

Author information

1
Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.

Abstract

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.

PMID:
17956728
DOI:
10.1016/j.cell.2007.08.028
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center