This review introduces the Mitochondrial-Stem Cell Connection (MSCC) hypothesis, suggesting that chronic oxidative phosphorylation (OxPhos) insufficiency in stem cells leads to the formation of cancer stem cells (CSCs) and drives tumorigenesis. The hypothesis explains metabolic alterations in cancer, where cells compensate for OxPhos deficiency by upregulating glycolysis and glutaminolysis. Dysfunctional
