Solmaz Kamrani, Mohammad Zaefizadeh, Khatereh Tooba

Abstract

Background: Cancer is a disease with uncontrollable growth in which cells gain some genetic changes to have unusual proliferation and growth. The tumor cells rely on glycolysis for ATP production. SDH and FH are practical in TCA cycle and ETC with production of intermediate sitrate (for macromolecules synthesis) and ROS (for signaling). Therefore, mitochondria participate in needs for signaling, biosynthesis and bioenergetics in cancer cells. The development of tumor cells damages mitochondrial functions therefore glycolysis is an essential mechanism against the decrease of ATP production from oxidative phosphorylation. Research Method: The related resources were searched and reviewed, and mutations in sites like Ensemble, and meta-analysis results in related references were identified. Findings: The analysis of the date showed that mitochondrial dysfunctions occurred due to the loss-of-function mutations in the TCA cycle enzymes (SDH, FH and IDH). Both of the SDH and FH were housekeeping genes, and had bioenergetics roles. IDH1 and IDH2 are heterodimer enzymes in cytoplasm and mitochondria; respectively, and produce NADPH by conversion of isositrate to α-ketoglutarate. It has been found that same mutations in IDH1 and IDH2 were linked with tumorigenesis. This mutation causes the IDH to achieve NADPH dependent enzymatic activity, and converses α-ketoglutarate to 2-hydroxi glutarate. In fact, this change causes the mutant enzymes to be redirected from NADPH production to NADPH consumption. Conclusion: It can be concluded that mutations in genes related to the conversion of C4 to C4 and C6 to C5 have a significant correlation with tumorgenesis.