Paradies Giuseppe, Paradies Valeria, Ruggiero Francesca M, Petrosillo Giuseppe
Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy,
Arch Toxicol. 2015 Jun;89(6):923-39. doi: 10.1007/s00204-015-1475-z. Epub 2015 Feb 18.
Mitochondria are the powerhouse of the eukaryotic cell through their use of oxidative phosphorylation to generate ATP. Mitochondrial dysfunction is considered an important contributing factor in a variety of physiopathological situations such as aging, heart ischemia/reperfusion injury, diabetes and several neurodegenerative and cardiovascular diseases, as well as in cell death. Increased formation of reactive oxygen species, altered respiratory chain complexes activity and opening of the mitochondrial permeability transition pore have been suggested as possible factors responsible for impaired mitochondrial function. Therefore, preventing mitochondrial dysfunction could be an effective therapeutic strategy against cellular degenerative processes. Cardiolipin is a unique phospholipid located at the level of inner mitochondrial membrane where it plays an important role in mitochondrial bioenergetics, as well as in cell death. Cardiolipin abnormalities have been associated with mitochondrial dysfunction in a variety of pathological conditions and aging. Melatonin, the major secretory product of the pineal gland, is a well-known antioxidant agent and thus an effective protector of mitochondrial bioenergetic function. Melatonin was reported to prevent mitochondrial dysfunction from oxidative damage by preserving cardiolipin integrity, and this may explain, at least in part, the beneficial effect of this compound in mitochondrial physiopathology. In this article, mechanisms through which melatonin exerts its protective role in mitochondrial dysfunction and related disorders are reviewed.
线粒体通过利用氧化磷酸化产生三磷酸腺苷（ATP），是真核细胞的动力源。线粒体功能障碍被认为是多种生理病理状况的重要促成因素，如衰老、心脏缺血/再灌注损伤、糖尿病以及几种神经退行性疾病和心血管疾病，还有细胞死亡。活性氧生成增加、呼吸链复合物活性改变以及线粒体通透性转换孔开放被认为是导致线粒体功能受损的可能因素。因此，预防线粒体功能障碍可能是对抗细胞退行性过程的有效治疗策略。心磷脂是一种独特的磷脂，位于线粒体内膜水平，在那里它在线粒体生物能量学以及细胞死亡中发挥重要作用。在各种病理状况和衰老过程中，心磷脂异常都与线粒体功能障碍有关。褪黑素是松果体的主要分泌产物，是一种著名的抗氧化剂，因此是线粒体生物能量功能的有效保护剂。据报道，褪黑素通过保持心磷脂完整性来预防线粒体功能障碍免受氧化损伤，这至少可以部分解释该化合物在线粒体生理病理学中的有益作用。本文综述了褪黑素在预防线粒体功能障碍及相关疾病中发挥保护作用的机制。
