Mechanisms of mitochondrial dysfunction in premature ovarian insufficiency

Premature ovarian insufficiency (POI) is a clinical syndrome characterized by the decline of ovarian function in women under the age of 40, and its core pathological feature is the irreversible depletion of the ovarian reserve. Mitochondria serve as the central hub for energy metabolism and signal integration in ovarian cells, and their dysfunction drives POI progression through multiple cell death pathways and signaling cascades. This review systematically examines the multidimensional mechanisms by which mitochondrial damage leads to follicle depletion and proposes, for the first time, an integrated regulatory model termed "mitochondrial damage - follicle fate decision." The review further identifies contradictory evidence, model limitations, and gaps in clinical translation within current research. Regarding therapeutic strategies, we evaluate the current status, safety risks, and ethical barriers of mitochondrial nutrients, stem cell therapy, gene editing, and mitochondrial replacement therapy. Finally, we propose a future research framework centered on mitochondrial dynamics and quality control, emphasizing the need for multi-omics integration and personalized interventions.