The Proapoptotic Effect of Melatonin on the Functioning of the Nonspecific Mitochondrial Pore (mPTP) in Rat Mitochondria

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.