Staying alive without oxidative phosphorylation

Staying alive without oxidative phosphorylation

Oxidative phosphorylation is used by many cell types to produce ATP, and requires a low-level constitutive flow of Ca2+ from the ER to the mitochondria. Cardenasand col.They found that this flow of Ca2+ is critical for the survival of defective cells in oxidative phosphorylation, a phenotype that is common in cancer cells. In the absence of oxidative phosphorylation, important metabolites can be generated through reducing carboxylation, a pathway that requires the Ca2+-sensitive enzyme α-ketoglutarate dehydrogenase (αKGDH) and NADH. Blocking the flow of Ca2+ from the ER into the mitochondria resulted in suppression of αKGDH activity, increased NAD+/NADH ratio, and improved autophagy, which failed to promote cell survival. These results highlight that the mitochondrial influx of Ca2+ regulates metabolic pathways in addition to oxidative phosphorylation and that it could be targeting specific types of cancer.

Source: stke.sciencemag.org