Mitochondrial epigenetic modifications and nuclear-mitochondrial communication: A new dimension towards understanding and attenuating the pathogenesis in women with PCOS

Mitochondrial DNA (mtDNA) epigenetic modifications have recently gained attention in a plethora of complex diseases, including polycystic ovary syndrome (PCOS), a common cause of infertility in women of reproductive age. Herein we discussed mtDNA epigenetic modifications and their impact on nuclear-mitochondrial interactions in general and the latest advances indicating the role of mtDNA methylation in the pathophysiology of PCOS. We highlighted epigenetic changes in nuclear-related mitochondrial genes, including nuclear transcription factors that regulate mitochondrial function and may be involved in the development of PCOS or its related traits. Additionally, therapies targeting mitochondrial epigenetics, including time-restricted eating (TRE), which has been shown to have beneficial effects by improving mitochondrial function and may be mediated by epigenetic modifications, have also been discussed. As PCOS has become a major metabolic disorder and a risk factor for obesity, cardiometabolic disorders, and diabetes, lifestyle/behavior intervention using TRE that reinforces feeding-fasting rhythms without reducing caloric intake may be a promising therapeutic strategy for attenuating the pathogenesis. Furthermore, future perspectives in the area of mitochondrial epigenetics are described.