Biological characteristics of ATP5A1 and its pathogenic mechanisms in human diseases: advances in clinical translation

Abstract

ATP5A1 acts as a crucial gene that encodes the core α subunit of the mitochondrial F1-ATPase complex to regulate cellular oxidative phosphorylation (OXPHOS) and maintain energy homeostasis. Consequently, its dysregulation—whether through aberrant expression, genomic alterations, or aberrant post-translational modifications—is hypothesized to be a key potential molecular event contributing to the pathogenesis of malignant tumors, neurodegenerative lesions, and metabolic dysregulation.This review systematically summarizes the molecular structure, biological functions, and regulatory networks of ATP5A1. A comprehensive overview of its expression patterns and pathogenic mechanisms across various diseases, including lung, colorectal, liver, and gastric cancers, as well as non-neoplastic conditions, is provided. Besides, emphasis is placed on the clinical translational potential of ATP5A1 as a diagnostic biomarker and therapeutic target, with recent advances in this area critically evaluated. Furthermore, current challenges and limitations in ATP5A1-related research are discussed, and future directions are proposed to facilitate mechanistic investigations and clinical applications. Collectively, this review establishes a comprehensive theoretical framework for understanding the role of ATP5A1 in disease pathogenesis and supports its potential utility in precision diagnostics and therapeutics.