Mitochondrial substrates in cancer: Drivers or passengers?

•Mitochondria play crucial role in various cell death modalities•Metabolic aberrations are hallmarks of cancer•Oncogenic switch in tumors alters the metabolism of various mitochondrial substrates•Targeting mitochondria is a promising strategy to combat cancer

The majority of cancers demonstrate various tumor-specific metabolic aberrations, such as increased glycolysis even under aerobic conditions (Warburg effect), whereas mitochondrial metabolic activity and their contribution to cellular energy production are restrained. One of the most important mechanisms for this metabolic switch is the alteration in the abundance, utilization, and localization of various mitochondrial substrates. Numerous lines of evidence connect disturbances in mitochondrial metabolic pathways with tumorigenesis and provide an intriguing rationale for utilizing mitochondria as targets for anti-cancer therapy.