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.