Cancer cells recovering from damage exhibit mitochondrial restructuring and increased aerobic glycolysis

• Some cancer cells recover from severe damage that causes cell death in majority of cells.
• Damage-Recovered (DR) cancer cells show reduced mitochondria, mDNA and mitochondrial enzymes.
• DR cells show increased aerobic glycolysis, ATP, cell proliferation, and resistance to damage.
• DR cells recovered from in vivo damage also show increased glycolysis and proliferation rate.

Instead of relying on mitochondrial oxidative phosphorylation, most cancer cells rely heavily on aerobic glycolysis, a phenomenon termed as “the Warburg effect”. We considered that this effect is a direct consequence of damage which persists in cancer cells that recover from damage. To this end, we studied glycolysis and rate of cell proliferation in cancer cells that recovered from severe damage. We show that in vitro Damage-Recovered (DR) cells exhibit mitochondrial structural remodeling, display Warburg effect, and show increased in vitro and in vivo proliferation and tolerance to damage. To test whether cancer cells derived from tumor microenvironment can show similar properties, we isolated Damage-Recovered (TDR) cells from tumors. We demonstrate that TDR cells also show increased aerobic glycolysis and a high proliferation rate. These findings show that Warburg effect and its consequences are induced in cancer cells that survive severe damage.