Figure 5.

Schematic illustration of SDHB deficiency-associated drug resistance. Left, mitochondrial complex I and II supply coenzyme Q with electron. Electron transport chain maintains mitochondrial membrane potential and ATP generation. Right, in cancer cells with SDHB genetic deficiency, the loss of mitochondrial complex II-derived electron results in dependency on complex I. Upregulated NADH dehydrogenase activity alters NAD⁺/ NADH balance, resulting in increased NAD⁺ availability and enhanced PARP DNA repair. Targeting NAD⁺/PARP DNA repair pathway sensitizes SDHB-deficient PCPG to genotoxic agent such as TMZ.