Abstract
Premature ovarian insufficiency (POI) is a common, heterogeneous disorder that affects up to 3.5% of women under 40 years of age and is defined by oligo/amenorrhoea, hypo-oestrogenism, and markedly elevated gonadotrophin levels. POI substantially increases risks for infertility, osteoporosis, cardiovascular disease, and psychological morbidity; however, its precise aetiology remains elusive, and current therapies rarely restore lasting ovarian function. This review synthesizes recent molecular, cellular, and animal data to clarify how six facets of mitochondrial dysregulation: oxidative stress, imbalanced dynamics (fusion/fission/mitophagy), defective biogenesis, altered mitochondrial DNA (copy-number and mutation), mitochondrial membrane potential, and disrupted electron-transport-chain activity-contribute to accelerated oocyte apoptosis, granulosa-cell dysfunction, and premature follicle loss. We further evaluate emerging mitochondria-targeted interventions, including small-molecule antioxidants, modulators of mitochondrial dynamics, biogenesis activators, autophagy regulators, mtDNA-protective agents, and innovative strategies such as mitochondrial transplantation. This article aims to systematically elaborate the mechanism of mitochondrial dysfunction in POI, summarize the treatment strategies for mitochondria, and provide a theoretical basis for clinical intervention.