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Kang, Byoung Heon
Cancer Biology Lab
Research Interests
  • Mitochondrial chaperones, cancer biology, cell death, metabolism, cancer stem cells, cancer therapeutics development

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

Cited 165 times inthomson ciCited 153 times inthomson ci
Title
Regulation of tumor cell mitochondrial Homeostasis by an organelle-specific Hsp90 chaperone network
Author
Kang, Byoung HeonPlescia, JanetDohi, TakehikoRosa, JackDoxsey, Stephen J.Altieri, Dario C.
Keywords
CELLBIO; HUMDISEASE; PROTEINS
Issue Date
2007-10
Publisher
CELL PRESS
Citation
CELL, v.131, no.2, pp.257 - 270
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.
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DOI
10.1016/j.cell.2007.08.028
ISSN
0092-8674
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BME_Journal Papers
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