Succinate Dehydrogenase and Ribonucleic Acid Networks in Cancer and Other Diseases

Abstract

Simple Summary

Although the dysfunction of the succinate dehydrogenase complex in mitochondria leads to cancer and other diseases due to aberrant metabolic reactions and signaling pathways, it is not well known how the succinate dehydrogenase complex is regulated. Our review highlights that non-coding ribonucleic acids (RNAs), RNA editing enzymes, and RNA modifying enzymes regulate expressions and functions of the succinate dehydrogenase complex. This research will provide new strategies for treating succinate dehydrogenase-relevant diseases in a clinic.

Abstract

Succinate dehydrogenase (SDH) complex connects both the tricarboxylic acid (TCA) cycle and the electron transport chain (ETC) in the mitochondria. However, SDH mutation or dysfunction-induced succinate accumulation results in multiple cancers and non-cancer diseases. The mechanistic studies show that succinate activates hypoxia response and other signal pathways via binding to 2-oxoglutarate-dependent oxygenases and succinate receptors. Recently, the increasing knowledge of ribonucleic acid (RNA) networks, including non-coding RNAs, RNA editors, and RNA modifiers has expanded our understanding of the interplay between SDH and RNA networks in cancer and other diseases. Here, we summarize recent discoveries in the RNA networks and their connections to SDH. Additionally, we discuss current therapeutics targeting SDH in both pre-clinical and clinical trials. Thus, we propose a new model of SDH–RNA network interaction and bring promising RNA therapeutics against SDH-relevant cancer and other diseases.