Research Highlights

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  • Cell & molecular biology

Published online: 20 February 2008 | doi:10.1038/nchina.2008.32

Chymotrypsin B: Not just a digestive protease

Jasmine Farsarakis

Introduction

© (2008) JBC

Mitochondria, through specific secretion of proteins, such as cytochrome c, are known to have a key regulatory role in apoptosis, the mechanism of cell death. Lysosomes are also known to have a role in the mitochondrial apoptotic process through protease secretion, but the exact mechanisms involved are not entirely understood. Fuyu Yang at the Chinese Academy of Sciences in Beijing¹ and co-workers show for the first time that chymotrypsin B, a digestive protease, also functions as a proapoptotic protease.

During their studies of mitochondrial membrane permeabilization in rat liver lysosomal extracts, the researchers encountered an unknown caspase — a type of calcium-dependent protease — with seemingly apoptotic properties. Subsequent purification of the unidentified protein showed that it was able to convert the proapoptotic protein Bid into truncated Bid at a neutral pH, inducing the secretion of cytochrome c by mitochondrial tissue. Further analyses confirmed that the unidentified protein was indeed chymotrypsin B, a protease known to be exclusively secreted by the pancreas.

The researchers conducted further studies into the apoptotic properties of lysosomal chymotrypsin B and observed that stimulation of lysosomal chymotrypsin B with tumour necrosis factor led to apoptotic cell death.

These results not only identify chymotrypsin B in rat liver lysosomes for the first time, but also demonstrate an intracellular proapoptotic function for the protease, indicating that chymotrypsin B may have a far more complex role in cellular processes than previously thought.

The authors of this work are from:
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; Advanced Mass Spectrometry Laboratory, University of North Texas Health Science Center, Fort Worth, Texas, USA; Graduate University of Chinese Academy of Sciences, Beijing, China.

Reference

1. Miao, Q. et al. Chymotrypsin B cached in rat liver lysosomes and involved in apoptotic regulation through a mitochondrial pathway. J. Biol. Chem. doi: 10.1074/jbc.M709789200 (2008). | Article |