Targeting mitochondria as an anticancer strategy

Mitochondrial metabolism and cancer development Mitochondria are organelles controlling adenosine triphosphate(ATP)generation,redox homeostasis,met-abolic signaling,and apoptotic pathways.Although gly-colysis was traditionally considered as the major source of energy in cancer cells,in-line with the so-called“Warburg effect”,mitochondria have been recognized to play a key role in oncogenesis[1].Cancer cells uniquely reprogram their cellular activities to support their rapid proliferation and migration,as well as to counteract met-abolic and genotoxic stress during cancer progression[2].Further,mitochondria can switch their metabolic phe-notypes to meet the challenges of high energy demand and macromolecular synthesis[3].Thus,cancer mito-chondria have the ability to flexibly switching between glycolysis and oxidative phosphorylation(OXPHOS)for their survival.The electron transport chain(ETC)func-tion is pivotal for mitochondrial respiration,which is also needed for dihydroorotate dehydrogenase(DHODH)activity that is essential for de novo pyrimidine synthe-sis[4].Recent researches have demonstrated that cancer cells devoid of mitochondrial DNA(mtDNA)lack their tumorigenic potential,and they re-gain this ability by acquiring healthy mtDNA from the host stromal cells via horizontal transfer of whole mitochondria[5,6]for recovery of the respiratory function.Functionally,respi-ration propels DHODH activity for pyrimidine biosyn-thesis[7].Therefore,targeting mitochondria holds great potential for anticancer strategy with high therapeutic opportunities.