Mitochondria and cancer

Abstract

Contrary to conventional wisdom, functional mitochondria are essential for the cancer cell. Although mutations in mitochondrial genes are common in cancer cells, they do not inactivate mitochondrial energy metabolism but rather alter the mitochondrial bioenergetic and biosynthetic state. These states communicate with the nucleus through mitochondrial ‘retrograde signalling’ to modulate signal transduction pathways, transcriptional circuits and chromatin structure to meet the perceived mitochondrial and nuclear requirements of the cancer cell. Cancer cells then reprogramme adjacent stromal cells to optimize the cancer cell environment. These alterations activate out-of-context programmes that are important in development, stress response, wound healing and nutritional status.

Glucose deprivation increases monocarboxylate transporter 1 (MCT1) expression and MCT1-dependent tumor cell migration

“…27 It is primarily achieved when TCs outgrow their oxygen and nutrient supply, marking the switch to a glycolytic metabolism. It is also typical of TCs constitutively addicted to glycolysis (the Warburg Effect).…”

Mitochondrial respiratory defects promote the Warburg effect and cancer progression

“…Mitochondrial DNA (mtDNA) defects such as mutations, deletions, and loss of copy number that result in defective electron transport chain complexes have been reported in a wide variety of cancers. 1,2 The causal role of mitochondrial defects in tumor formation has not been established; however, using hybrid cell technology to replace endogenous mtDNA with that from tumor cell lines, the role of mtDNA mutations of Complex I, III, and V subunits in inducing tumorigenic cellular transformations has been demonstrated. [2][3][4] Moreover, defects in nuclear encoded mitochondrial proteins such as succinate dehydrogenase, fumarate hydratase, and isocitrate dehydrogenase have been shown to lead to accumulation of oncometabolites and are directly implicated in specific cancers.…”

Mitochondrial dysfunction in breast cancer cells prevents tumor growth

“…[1][2][3][4][5][6][7][8] Although it is generally agreed upon that cancer cells undergo metabolic re-programming, [1][2][3][4][5][6][7][8] the exact nature of these metabolic changes varies widely, and has not previously been correlated with clinical outcome in cancer patients.…”