Abstract：As a mitochondria-targeted antioxidant, mitoquinone mesylate (MitoQ) has been proved to relieve oxidative stress damage of mitochondria, target mitochondria to resist apoptosis, and maintain body health. Existing research has proven that MitoQ plays an important role in cell damage, organ damage repair and the treatment of various diseases. This paper reviews the biological functions of MitoQ such as antioxidant, resistance to cell inflammation and apoptosis, and its mitochondrial targeting, and systematically summarizes the research progress of MitoQ in the treatment of neurodegenerative diseases, cardiovascular injury, metabolic organ injury, and diabetes. This review provides reference for the use of MitoQ in cell biology and clinical disease treatment.
[1] 谭宁, 李巴仑, 韩苗, 等. 2024.米托蒽醌甲磺酸盐预处理脂肪间充质干细胞对犬糖尿病的治疗效果评价[J]. 畜牧兽医学报, 55(3): 1328-1344. (Tan N, Li B, Han M, et al., 2024. Evaluation of therapeutic effect of mitoquionl mesylate pretreated adipose derived mesenchymal stem cells on canine diabetes mellitus[J]. Acta Veterinaria et Zootechnica Sinica, 55(3): 1328-1344. [2] 钟丽君, 邓嘉强, 古丛伟, 等. 2022. MitoQ对犬骨髓间充质干细胞线粒体功能及抗氧化能力的影响[J].浙江农业学报, 34(05): 934-941. (Zhong L, Deng J, Gu C, et al., 2022. Effects of MitoQ on mitochondrial function and antioxidant capacity of canine bone marrow mesenchymal stem cells[J]. Acta Agriculturae Zhejiangensis, 34(5): 934-941). [3] 周家奇, 高静, 方强. 2022. 线粒体辅酶Q通过PI3K/Akt途径减轻脂多糖诱导的Ⅱ型肺泡上皮细胞线粒体依赖性凋亡[J]. 中华危重病急救医学, 34(4): 378-382. (Zhou J, Gao J, Fang Q.2022. Mitochondrial coenzyme Q attenuates lipopolysaccharide-induced mitochondria-dependent apoptosis in type II alveolar epithelial cells via phosphatidylinositol 3-kinase/Akt pathway[J]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue, 34(4): 378-382.) [4] Adlam V J, Harrison J C, Porteous C M, et al., 2005. Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury[J]. The FASEB Journal, 19(9): 1088-1095. [5] Bolognesi M L, Matera R, Minarini A, et al., 2009. Alzheimer's disease: New approaches to drug discovery[J]. Current Opinion in Chemical Biology, 13(3): 303-308. [6] Capeloa T, Van de Velde J A, d'Hose D, et al., 2022. Inhibition of mitochondrial redox signaling with MitoQ prevents metastasis of human pancreatic cancer in mice[J]. Cancers (Basel), 14(19): 4918. [7] Cocheme H M, Kelso G F, James A M, et al., 2007. Mitochondrial targeting of quinones: Therapeutic implications[J]. Mitochondrion, 7(Suppl): S94-102. [8] Escribano-Lopez I, Banuls C, Diaz-Morales N, et al., 2019. The mitochondria-targeted antioxidant MitoQ modulates mitochondrial function and endoplasmic reticulum stress in pancreatic beta cells exposed to hyperglycaemia[J]. Cellular Physiology and Biochemistry, 52(2): 186-197. [9] Escribano-Lopez I, Diaz-Morales N, Rovira-Llopis S, et al., 2016. The mitochondria-targeted antioxidant MitoQ modulates oxidative stress, inflammation and leukocyte-endothelium interactions in leukocytes isolated from type 2 diabetic patients[J]. Redox Biology, 10: 200-205. [10] Gan L, Wang Z, Si J, et al., 2018. Protective effect of mitochondrial-targeted antioxidant MitoQ against iron ion (56)Fe radiation induced brain injury in mice[J]. Toxicology and Applied Pharmacology, 341: 1-7. [11] Gioscia-Ryan R A, LaRocca T J, Sindler A L, et al., 2014. Mitochondria-targeted antioxidant (MitoQ) ameliorates age-related arterial endothelial dysfunction in mice[J]. The Journal of Physiology, 592(12): 2549-2561. [12] Han Y, Xu X, Tang C, et al., 2018. Reactive oxygen species promote tubular injury in diabetic nephropathy: The role of the mitochondrial ros-txnip-nlrp3 biological axis[J]. Redox Biology, 16: 32-46. [13] Imai Y, Fink B D, Promes J A, et al., 2018. Effect of a mitochondrial-targeted coenzyme Q analog on pancreatic beta-cell function and energetics in high fat fed obese mice[J]. Pharmacology Research & Perspectives, 6(3): e00393. [14] Ismail H, Shakkour Z, Tabet M, et al., 2020. Traumatic brain injury: Oxidative stress and novel anti-oxidants such as mitoquinone and edaravone[J]. Antioxidants (Basel), 9(10): 943. [15] Jou M J.2008. Pathophysiological and pharmacological implications of mitochondria-targeted reactive oxygen species generation in astrocytes[J]. Advanced Drug Delivery Reviews, 60(13-14): 1512-1526. [16] Keck F, Khan D, Roberts B, et al., 2018. Mitochondrial-directed antioxidant reduces microglial-induced inflammation in murine in vitro model of TC-83 infection[J]. Viruses, 10(11): 606. [17] Liang S, Tian X, Wang C.2022. Nanozymes in the treatment of diseases caused by excessive reactive oxygen specie[J]. Journal of Inflammation Research, 15: 6307-6328. [18] Mantle D, Hargreaves I P.2022. Coenzyme Q10: Role in less common age-related disorders[J]. Antioxidants (Basel), 11(11): 2293. [19] Mao H, Zhang Y, Xiong Y, et al., 2022. Mitochondria-targeted antioxidant mitoquinone maintains mitochondrial homeostasis through the Sirt3-dependent pathway to mitigate oxidative damage caused by renal ischemia/reperfusion[J]. Oxidative Medicine and Cellular Longevity, 2022: 2213503. [20] Miao J, Liu J, Niu J, et al., 2019. Wnt/beta-catenin/RAS signaling mediates age-related renal fibrosis and is associated with mitochondrial dysfunction[J]. Aging Cell, 18(5): e13004. [21] Oliver D M A, Reddy P H.2019. Small molecules as therapeutic drugs for Alzheimer's disease[J]. Molecular and Cellular Neuroscience, 96: 47-62. [22] Piscianz E, Tesser A, Rimondi E, et al., 2021. MitoQ is able to modulate apoptosis and inflammation[J]. International Journal of Molecular Sciences, 22(9) [23] Prauchner C A.2017. Oxidative stress in sepsis: Pathophysiological implications justifying antioxidant co-therapy[J]. Burns, 43(3): 471-485. [24] Ramis M R, Esteban S, Miralles A, et al., 2015. Protective effects of melatonin and mitochondria-targeted antioxidants against oxidative stress: A review[J]. Current Medicinal Chemistry, 22(22): 2690-2711. [25] Reddy P H.2006. Mitochondrial oxidative damage in aging and Alzheimer's disease: implications for mitochondrially targeted antioxidant therapeutics[J]. Journal of Biomedicine and Biotechnology, 2006(3): 31372. [26] Ribeiro Junior R F, Dabkowski E R, Shekar K C, et al., 2018. MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload[J]. Free Radical Biology and Medicine, 117: 18-29. [27] Shan S, Liu Z, Liu Z, et al., 2022. MitoQ alleviates carbon tetrachloride-induced liver fibrosis in mice through regulating JNK/YAP pathway[J]. Toxicology Research (Camb), 11(5): 852-862. [28] Shang Y, Xue W, Kong J, et al., 2022. Ultrafine black carbon caused mitochondrial oxidative stress, mitochondrial dysfunction and mitophagy in SH-SY5Y cells[J]. Science of The Total Environment, 813: 151899. [29] Smith R A, Murphy M P.2010. Animal and human studies with the mitochondria-targeted antioxidant MitoQ[J]. Annals of the New York Academy of Sciences, 1201: 96-103. [30] Subramanian S, Kalyanaraman B, Migrino R Q.2010. Mitochondrially targeted antioxidants for the treatment of cardiovascular diseases[J]. Recent Patents on Cardiovascular Drug Discovery, 5(1): 54-65. [31] Supinski G S, Murphy M P, Callahan L A.2009. MitoQ administration prevents endotoxin-induced cardiac dysfunction[J]. American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 297(4): R1095-R1102. [32] Ünal İ, Çalışkan-Ak E, Üstündağ Ü V, et al., 2020. Neuroprotective effects of mitoquinone and oleandrin on Parkinson's disease model in zebrafish[J]. International Journal of Neuroscience, 130(6): 574-582. [33] Xi Y, Feng D, Tao K, et al., 2018. MitoQ protects dopaminergic neurons in a 6-OHDA induced PD model by enhancing Mfn2-dependent mitochondrial fusion via activation of PGC-1α[J]. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1864(9 Pt B): 2859-2870. [34] Young M L, Franklin J L.2019. The mitochondria-targeted antioxidant MitoQ inhibits memory loss, neuropathology, and extends lifespan in aged 3xTg-AD mice[J]. Molecular and Cellular Neuroscience, 101: 103409. [35] Zhan P, Lu X, Li Z, et al., 2022. Mitoquinone alleviates bleomycin-induced acute lung injury via inhibiting mitochondrial ROS-dependent pulmonary epithelial ferroptosis[J]. International Immunopharmacology, 113(Pt A): 109359.
