Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 72, Issue 24, Pages 4807-4824Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-015-2039-3
Keywords
LONP1; Pim1; Mitochondria; Hypoxia; mtDNA
Categories
Funding
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [11341]
- National Basic Research Program of China (973 Program) [2013CB531700]
- National Natural Science Foundation of China [31070710, 31171345]
- Zhejiang Qianjiang Talent Project B [2010R10045]
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Lon protease is a nuclear DNA-encoded mitochondrial enzyme highly conserved throughout evolution, involved in the degradation of damaged and oxidized proteins of the mitochondrial matrix, in the correct folding of proteins imported in mitochondria, and in the maintenance of mitochondrial DNA. Lon expression is induced by various stimuli, including hypoxia and reactive oxygen species, and provides protection against cell stress. Lon down-regulation is associated with ageing and with cell senescence, while up-regulation is observed in tumour cells, and is correlated with a more aggressive phenotype of cancer. Lon up-regulation contributes to metabolic reprogramming observed in cancer, favours the switch from a respiratory to a glycolytic metabolism, helping cancer cell survival in the tumour microenvironment, and contributes to epithelial to mesenchymal transition. Silencing of Lon, or pharmacological inhibition of its activity, causes cell death in various cancer cells. Thus, Lon can be included in the growing class of proteins that are not responsible for oncogenic transformation, but that are essential for survival and proliferation of cancer cells, and that can be considered as a new target for development of anticancer drugs.
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