Esteban-Amo María J, Jiménez-Cuadrado Patricia, Serrano-Lorenzo Pablo, de la Fuente Miguel Á, Simarro María
Department of Cell Biology, Genetics, Histology and Pharmacology, Faculty of Medicine, University of Valladolid, 47005 Valladolid, Spain.
Unit of Excellence Institute of Biomedicine and Molecular Genetics (IBGM), University of Valladolid and Spanish National Research Council (CSIC), 47003 Valladolid, Spain.
Biomedicines. 2024 Sep 9;12(9):2050. doi: 10.3390/biomedicines12092050.
Succinate dehydrogenase (also known as complex II) plays a dual role in respiration by catalyzing the oxidation of succinate to fumarate in the tricarboxylic acid (TCA) cycle and transferring electrons from succinate to ubiquinone in the mitochondrial electron transport chain (ETC). Owing to the privileged position of SDH/CII, its dysfunction leads to TCA cycle arrest and altered respiration. This review aims to elucidate the widely documented profound metabolic effects of SDH/CII deficiency, along with the newly unveiled survival mechanisms in SDH/CII-deficient cells. Such an understanding reveals exploitable vulnerabilities for strategic targeting, which is crucial for the development of novel and more precise therapies for primary mitochondrial diseases, as well as for familial and sporadic cancers associated with SDH/CII mutations.
琥珀酸脱氢酶（也称为复合体II）在呼吸作用中发挥双重作用，它在三羧酸（TCA）循环中催化琥珀酸氧化为延胡索酸，并在线粒体电子传递链（ETC）中将电子从琥珀酸传递给泛醌。由于琥珀酸脱氢酶/复合体II的特殊地位，其功能障碍会导致TCA循环停滞和呼吸作用改变。本综述旨在阐明已被广泛记录的琥珀酸脱氢酶/复合体II缺乏所产生的深远代谢影响，以及新发现的琥珀酸脱氢酶/复合体II缺乏细胞中的存活机制。这样的理解揭示了可用于战略靶向的可利用弱点，这对于开发针对原发性线粒体疾病以及与琥珀酸脱氢酶/复合体II突变相关的家族性和散发性癌症的新型且更精确的疗法至关重要。
