Frontiers in LONP1 research: Unraveling molecular mechanisms, disease associations, and therapeutic strategies

Abstract

LONP1 is a conserved mitochondrial AAA + protease central to mitochondrial proteostasis. This review summarizes its structural features, protease-chaperone functions, and roles in metabolic regulation (heme/sulfur/steroid pathways) and disease. In cancer, LONP1 overexpression drives tumor progression via metabolic reprogramming, EMT induction, metastasis, and therapy resistance, establishing it as a pan-cancer therapeutic target. Inhibitors face delivery and selectivity challenges, prompting future strategies like mitochondrial-targeted delivery and allosteric modulators. Research directions include mechanistic studies and clinical translation for cancer and neurodegenerative disorders.