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The effect of the cytostatic antitumor drug ONC201 on the number of mitochondrial nucleoids and the average size of mitochondria in the BT474 human breast cancer cells was studied. It was shown that incubation of BT474 cells with ONC201 (10 μM) for 24 h reduces the number of nucleoids from 262 ± 46 to 140 ± 27 per cell, and the number of mitochondrial nucleoids was further reduced to 67 ± 22 per cell in cells incubated with the drug for 48 h. It was found that the ONC201-induced change in the number of nucleoids per cell depended on the duration of the presence of the agent in the incubation medium. Short-term (24 h) and long-term (48 h) exposure of cells to a single dose of ONC201 led to a reversible and irreversible change in the number of nucleoids per cell, respectively. Thus, after 24 h of exposure and subsequent 120 h washout with ONC201-free medium, the number of nucleoids was restored to 211 ± 47 per cell, while 120-h washout of the drug after 48 h of treatment did not lead to the restoration of the number of nucleoids, and their number remained at the level of 70 ± 59 per cell. Changes in the number of mitochondrial nucleoids, regardless of the duration of cell treatment with ONC201, positively correlated with changes in the average size of mitochondria as an indicator of their morphology. It is concluded that ONC201 has a cytostatic effect on BT474 cells in culture, suppresses cell proliferation, and induces a reversible or irreversible decrease in the number of mitochondrial nucleoids and fragmentation of mitochondria, depending on the duration of treatment.