
Targeting mitochondria as an anticancer strategy
Author(s) -
Dong Lanfeng,
Neuzil Jiri
Publication year - 2019
Publication title -
cancer communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.119
H-Index - 53
ISSN - 2523-3548
DOI - 10.1186/s40880-019-0412-6
Subject(s) - mitochondrion , oxidative phosphorylation , warburg effect , biology , microbiology and biotechnology , citric acid cycle , cancer cell , glycolysis , respiratory chain , biochemistry , cancer , metabolism , genetics
Mitochondria are organelles controlling adenosine triphosphate (ATP) generation, redox homeostasis, metabolic signaling, and apoptotic pathways. Although glycolysis 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 metabolic and genotoxic stress during cancer progression [2]. Further, mitochondria can switch their metabolic phenotypes to meet the challenges of high energy demand and macromolecular synthesis [3]. Thus, cancer mitochondria have the ability to flexibly switching between glycolysis and oxidative phosphorylation (OXPHOS) for their survival. The electron transport chain (ETC) function is pivotal for mitochondrial respiration, which is also needed for dihydroorotate dehydrogenase (DHODH) activity that is essential for de novo pyrimidine synthesis [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, respiration propels DHODH activity for pyrimidine biosynthesis [7]. Therefore, targeting mitochondria holds great potential for anticancer strategy with high therapeutic opportunities.