{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ATP5ME is a nuclear‐encoded subunit of the mitochondrial ATP synthase (complex V) that plays a critical role in the enzyme’s assembly and stability and is essential for efficient ATP production via oxidative phosphorylation. Altered expression or regulation of ATP5ME (also referenced as ATP5I in several studies) has emerged as an important factor in diverse pathological settings. For example, in colorectal cancer, post‐transcriptional mechanisms mediated by RNA‐binding proteins such as RALY promote the processing of specific microRNAs that systematically downregulate several mitochondrial ATP synthase subunits—including ATP5ME—resulting in reprogramming of mitochondrial metabolism that supports tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Similarly, in models of drug‐induced and developmental cardiotoxicity, reduced levels of ATP synthase subunits are associated with impaired mitochondrial membrane potential and diminished ATP synthesis, thereby contributing to decreased cellular energy supply."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In reproductive studies, decreased expression of ATP5ME/ATP5I in human mural granulosa cells correlates with mitochondrial dysfunction and lower intracellular ATP levels, conditions that become more pronounced with advanced maternal age and which may negatively affect oocyte quality and follicular health."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, in experimental models of aging and hormone‐modulated brain function, altered expression of multiple complex V components—including ATP5ME—is linked to compromised mitochondrial complex V activity and impaired energy homeostasis in critical brain regions that regulate motor behavior."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Finally, genomic analyses of chromosomal aberrations have identified deletions encompassing ATP5ME among other genes, further underscoring its importance in maintaining normal mitochondrial function and cellular energy balance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lei Sun, Arabella Wan, Zhuolong Zhou, et al. 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