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Mitochondrial Lon Protease and Cancer

Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1038)

Abstract

ATP-dependent Lon protease of mitochondrial matrix is encoded by nuclear DNA and highly evolutionarily conserved throughout all organisms, which is involved in the quality control of proteins by selective degradation of misfolded, oxidized, and short-lived regulatory proteins within mitochondrial matrix, maintenance of mitochondrial genome (mtDNA), and folding of mitochondria proteins. Various stimuli such as hypoxia and oxidative and ER stress lead to upregulation of Lon expression. Inhibition of protease activity or downregulation of Lon promotes cancer cell death and enhances sensitivity of cancer cells to anticancer drugs through metabolic reprogramming, thus reducing the viability of cancer cell in tumor microenvironment and epithelial to mesenchymal transition (EMT). Moreover, mitochondrial ATP-dependent Lon protease may serve as a potential biomarker for cancer diagnosis and novel target for the development of anticancer drugs and for predicting of the efficiency and effectiveness of chemotherapy of a variety of cancers.

Keywords

Mitochondria Lon Cancer Protein quality control Protein degradation Anticancer drug 

Notes

Acknowledgments

Many thanks to Carolyn K. Suzuki and the members in my laboratory. This study has been supported by grants from the National Basic Research Program of China (973 Program, No. 2013CB531700), National Natural Science Foundation of China (No. 31070710, No. 31171345, No. 31570772, No. 31771543), and Zhejiang Qianjiang Talent Project B (No. 2010R10045) to BL.

Conflicting Declaration

No.

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Copyright information

© The Editor(s) (if applicable) and The Author(s) 2018 2017

Authors and Affiliations

  1. 1.Institute of Biophysics, Attardi Institute of Mitochondrial Biomedicine and Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life SciencesWenzhou Medical UniversityWenzhouChina

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