Mitochondria are the key source of energy in cells. In a cancer cell,
mitochondrial metabolism is deregulated to compensate for the energy requirements of
the dividing cells. Mitochondria play a significant role in apoptosis by releasing the
pro-apoptotic factors, which are also altered in cancer cells. In this context, the role of
mitochondrial bioenergetics in regulating cancer stem cells, chemoresistance, and
malignant transformation is just beginning to be unraveled. Additionally, mutations in
mitochondrial enzymes can result in oncometabolite production, which acts as signal
transducers that help in tumour growth. Mitochondria also play an important role in
immune system evasion by altering the tumour microenvironment. All these make
mitochondria a key target for cancer therapy. The mitochondrial outer membrane
protein BCL2 is an anti-apoptotic protein against which a small-molecule inhibitor,
Venetoclax, has been approved to treat leukaemia. Arsenic trioxide, a small-molecule
inhibitor that targets complex IV in the inner membrane, has been approved by the US
FDA to treat acute promyelocytic leukaemia. Metformin, a complex I inhibitor of the
electron-transport chain, has shown a better effect on cancers having a mutation in
complex I genes. Several drugs that can modulate the mitochondrial dynamics and
functions are being tested for their anticancer property. This chapter discusses the
mitochondrial functions in normal cells versus those in cancer cells and cancer stem
cells. Anticancer therapy targeting mitochondrial proteins and processes is also
elaborated. A catalogue of known mitochondrial mutations involved in cancer is
presented. Immunotherapy using mutated mitochondrial proteins or peptides and
immunometabolism as a target for cancer therapy is also discussed.
Keywords: BCL2, Cancer stem cells, Genome, Membrane, Metabolism,
Mitochondria, Mutations, Therapy, Transcriptome.
