Itaconic acid (methylene-succinic acid, ItA) is an unsaturated dicarboxylic acid that is secreted by mammalian macrophages in response to a pro-inflammatory stimulus and shows an anti-inflammatory/antibacterial effect. Being a mitochondrial metabolite, it exhibits an inhibitory activity on succinate dehydrogenase and subsequently induces mitochondrial dysfunction. The present study has shown that ItA dose-dependently inhibited ADP- and DNP-stimulated (uncoupled) respiration of rat liver mitochondria energized with succinate. This effect of ItA could be related to the suppression of the activity of complex II and the combined activity of complexes II + III of the respiratory chain. At the same time, ItA had no effect on the activity of the dicarboxylate carrier, which catalyzes the transport of succinate across the inner mitochondrial membrane. It was found that 4 mM ItA diminished the rates of ADP- and DNP-stimulated mitochondrial respiration supported by the substrates of complex I glutamate and malate. A study of the effect of ItA on the activity of complexes of the respiratory chain showed that it decreases the activity of complex IV. It was observed that 4 mM ItA inhibited the rate of H₂O₂ production by mitochondria. At the same time, ItA promoted the opening of the cyclosporin A-sensitive Ca²⁺-dependent permeability transition pore. The latter was revealed as the decrease in the calcium retention capacity of mitochondria and the stimulation of release of cytochrome c from the organelles. ItA by itself promoted the cytochrome c release from mitochondria. Possible mechanisms of the effect of ItA on mitochondrial function are discussed.

衣康酸（亚甲基琥珀酸，ItA）是不饱和二羧酸，其响应促炎刺激由哺乳动物巨噬细胞分泌，并显示出抗炎/抗菌作用。作为线粒体代谢产物，它对琥珀酸脱氢酶表现出抑制活性，并随后诱发线粒体功能障碍。本研究表明，ItA剂量依赖性地抑制了琥珀酸盐激发的大鼠肝线粒体的ADP和DNP刺激的（非偶联）呼吸作用。ItA的这种作用可能与抑制呼吸道复合物II的活性以及复合物II + III的联合活性有关。同时，ItA对二羧酸盐载体的活性没有影响，后者催化琥珀酸跨线粒体内膜的运输。发现4 mM ItA降低了由复合谷氨酸和苹果酸底物支持的ADP和DNP刺激的线粒体呼吸的速率。对ItA对呼吸链复合物活性的影响的研究表明，它降低了复合物IV的活性。观察到4 mM ItA抑制H的速率线粒体产生₂ O ₂。同时，ItA促进了环孢菌素A敏感的Ca ²⁺依赖性渗透性过渡孔的开放。后者被揭示为线粒体钙保留能力的降低和细胞色素c从细胞器释放的刺激。ItA本身促进了线粒体中细胞色素c的释放。讨论了ItA影响线粒体功能的可能机制。