Mitochondrial Quality Control: A Gatekeeper of Spermatogenesis

Male infertility is rising worldwide. Spermatogenesis is energetically demanding and tightly coupled to mitochondrial quality control (MQC)-including biogenesis, fusion-fission dynamics, and mitophagy. Here we synthesize current evidence across developmental stages of germ cells, highlighting stage-specific shifts from glycolysis-supported ATP production to oxidative phosphorylation (OXPHOS)-dominated metabolism and remodeling of mitochondrial architecture into the midpiece sheath. We summarize genetic and functional data implicating OPA1/MFN1-2 in inner/outer membrane fusion, DRP1/FIS1/MFF in fission and sheath organization, and the roles of PINK1-Parkin-dependent and -independent mitophagy in mitochondrial quality control, while acknowledging that cytoplasm removal and acrosome maintenance during spermiogenesis may involve general autophagy rather than mitophagy specifically. Mitochondrial dysfunction-excess reactive oxygen species (ROS), mitochondrial membrane potential (MMP) collapse, dysregulated dynamics, or defective mitophagy-impairs spermatogenesis and sperm function. We also identify methodological gaps that limit translation, particularly the lack of standardized phenotyping and human genetic evidence. Clarifying MQC causality and druggability may support future diagnostic or therapeutic research in male infertility.