Melatonin (MEL) is a hormone produced by the pineal gland. It easily penetrates the cell membrane and may be accumulated in the mitochondria at high concentrations and improve their functional state. However, there are also data that show that the effect of MEL on mitochondria may greatly vary, i.e., it depends on the type of tissue, the conditions of administration, and the composition and structural features of the target molecules. In the present work, we studied the effect of MEL on the functional state of rat brain mitochondria when it is directly added to mitochondria under conditions of opening of the nonspecific mito-chondrial permeability transition pore (mPTP), as well as the effects on the levels of mPTP regulators (VDAC and CNPase) and the main subunits of the electron transport chain (ETC). It was found that the direct addition of MEL at a concentration of 10 nM and 100 nM to mitochondria leads to a change in the protein level of the first and fourth ETC complexes, initiation of mPTP opening, as well as a decrease in the levels of proteins that regulate mPTP function. These data suggest that MEL may act as a pro-apoptotic agent, which may have important biological and pharmacological significance.

中文翻译：

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褪黑素对大鼠线粒体非特异性线粒体孔（mPTP）功能的促凋亡作用

褪黑激素（MEL）是松果体产生的一种激素。它很容易穿透细胞膜，并可能以高浓度积聚在线粒体中并改善其功能状态。但是，也有数据表明MEL对线粒体的作用可能会发生很大变化，即，它取决于组织的类型，给药条件以及靶分子的组成和结构特征。在本工作中，我们研究了在非特异性线粒体通透性转换孔（mPTP）打开的条件下，将MEL直接添加到线粒体中时，MEL对大鼠脑线粒体功能状态的影响，以及对MEL的影响。 mPTP调节剂（VDAC和CNPase）的水平和电子传输链（ETC）的主要亚基。已发现直接向线粒体中添加浓度为10 nM和100 nM的MEL会导致第一和第四ETC复合物的蛋白质水平发生变化，mPTP开启的开始以及MCP的水平降低调节mPTP功能的蛋白质。这些数据表明，MEL可能是促凋亡剂，可能具有重要的生物学和药理学意义。