Su Tong, Zhu Li Han, Liu Jun Xian, Jin Li Yuan, Cui Huixing, Yu Longhao, Zhang Yin Hua
Yanbian University College of Medicine, Yanbian University Hospital, Yanji 133000, China.
Department of Physiology & Biomedical Sciences, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
Biomolecules. 2025 Aug 20;15(8):1197. doi: 10.3390/biom15081197.
Hydrogen sulfide (HS) has been established to regulate mitochondrial respiration and ATP production, but whether the regulation is through -sulfhydration (-SSH) of mitochondrial complexes is not well understood. Recently, HS is known to exert diverse and dose-dependent effects on mitochondrial complexes. However, the involvement of -sulfhydration of each mitochondrial complex and the activities in diabetic hearts have not been revealed. Here, we conducted comprehensive investigations into -sulfhydration and the activities of mitochondrial complexes I-V in normal and Streptozotocin (STZ)-induced type 1 diabetic (DM) heart mitochondria. Results showed that proteins of HS-producing enzymes were downregulated in DM heart mitochondria, which was accompanied by reduced mitochondrial membrane potential (MMP), greater ROS, and lower complex I and V activities, reduced complex V-SSH in DM. In both groups, supplementation with the HS donor NaHS increased the -sulfhydration of all mitochondrial complexes, and the activities of complexes I-III and V were significantly increased but complex IV activity was reduced. Consequently, mitochondrial MMP, ROS, and ATP production were normalized with NaHS in DM, whereas inhibition of HS generation increased mitochondrial ROS and reduced MMP via reducing complex activities in both groups. Ischemic reperfusion did not affect NaHS-increment of -sulfhydration of complexes I-V, but significantly impaired complex V activity in DM. Collectively, HS-dependent -sulfhydration of mitochondrial complexes I-V in normal and DM heart mitochondria were involved in the activation of mitochondrial complexes I-III/V and the inhibition of complex IV, which control cardiac mitochondrial respiration and ATP production.
硫化氢（HS）已被证实可调节线粒体呼吸和ATP生成，但这种调节是否通过线粒体复合物的巯基化（-SSH）实现尚不清楚。最近，已知HS对线粒体复合物具有多种剂量依赖性作用。然而，每种线粒体复合物的巯基化参与情况以及在糖尿病心脏中的活性尚未揭示。在此，我们对正常和链脲佐菌素（STZ）诱导的1型糖尿病（DM）心脏线粒体中复合物I-V的巯基化及其活性进行了全面研究。结果表明，DM心脏线粒体中产生HS的酶蛋白下调，同时伴有线粒体膜电位（MMP）降低、活性氧增加以及复合物I和V活性降低，DM中复合物V的SSH减少。在两组中，补充HS供体NaHS均增加了所有线粒体复合物的巯基化，复合物I-III和V的活性显著增加，但复合物IV的活性降低。因此，DM中NaHS使线粒体MMP、活性氧和ATP生成恢复正常，而抑制HS生成则通过降低两组中的复合物活性增加线粒体活性氧并降低MMP。缺血再灌注不影响NaHS对复合物I-V巯基化的增加，但显著损害DM中复合物V的活性。总体而言，正常和DM心脏线粒体中依赖HS的复合物I-V巯基化参与了线粒体复合物I-III/V的激活和复合物IV的抑制，从而控制心脏线粒体呼吸和ATP生成。
