Medical Biophysics

New study co-led by Dr. Aaron Schimmer

May 13, 2019

Diagram from Dr. Schimmer publication

MBP researcher Dr. Aaron Schimmer and his fellow research collaborators have released a new article published in Cancer Cell titled "Mitochondrial ClpP-Mediated Proteolysis Induces Selective Cancer Cell Lethality".

The mitochondrial caseinolytic protease P (ClpP) plays a central role in mitochondrial protein quality control by degrading misfolded proteins. Using genetic and chemical approaches, Dr. Schimmer and his team showed that hyperactivation of the protease selectively kills cancer cells, independently of p53 status, by selective degradation of its respiratory chain protein substrates and disrupts mitochondrial structure and function, while it does not affect non-malignant cells. Dr. Schimmer's and his collaborators identified imipridones as potent activators of ClpP. Through biochemical studies and crystallography, they show that imipridones bind ClpP non-covalently and induce proteolysis by diverse structural changes. Imipridones are presently in clinical trials. Their findings suggest a general concept of inducing cancer cell lethality through activation of mitochondrial proteolysis.

Read the article.

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