Figure 1.

Mitochondrial retrograde signaling induced by cytochrome c oxidase dysfunction promotes the Warburg effect. Cytochrome c oxidase (CcO) defects can be effected by genetic mutations and oxidative damage to susceptible subunits by environmental factors and hypoxia. Retrograde signaling is activated by loss of membrane potential and induction of calcineurin. Stress-induced transcription factors induce gene expression and metabolic reprogramming leading to cell survival and extracellular matrix (ECM) modulation.