Tang Pei, Zeng Qun, Li Yihao, Wang Jing, She Meihua
Department of Biochemistry and Molecular Biology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421000, P.R. China.
Hengyang Medical School, University of South China, Hengyang, Hunan, 421000, P.R. China.
Mol Biol Rep. 2025 Apr 18;52(1):401. doi: 10.1007/s11033-025-10500-8.
Lon peptidase 1 (LONP1), a member of the AAA + family, is essential for maintaining mitochondrial function. Recent studies have revealed that LONP1 serves as a multifunctional enzyme, acting not only as a protease but also as a molecular chaperone, interacting with mitochondrial DNA (mtDNA), and playing roles in mitochondrial dynamics, oxidative stress, cellular respiration, and energy metabolism. LONP1 is evolutionarily highly conserved, and mutations or dysfunctions in LONP1 can lead to diseases. There is growing evidence linking LONP1 to various human diseases, such as tumors, neurodegenerative diseases, and heart diseases. This review discusses the discovery, molecular structure, subcellular localization, tissue distribution, and mitochondrial function of LONP1. Furthermore, it summarizes the associations between LONP1 and tumors, neurodegenerative diseases, and heart diseases, exploring its role in different diseases and potential molecular mechanisms. It also analyzes the regulatory effects of related inhibitors and agonists on LONP1. Considering the pleiotropic effects of LONP1, the study of LONP1 is crucial to understanding the relevant pathophysiological processes and developing strategies to modulate and control these related diseases.
LON 肽酶 1（LONP1）是 AAA + 家族的成员之一，对维持线粒体功能至关重要。最近的研究表明，LONP1 是一种多功能酶，不仅作为蛋白酶发挥作用，还作为分子伴侣，与线粒体 DNA（mtDNA）相互作用，并在线粒体动力学、氧化应激、细胞呼吸和能量代谢中发挥作用。LONP1 在进化上高度保守，LONP1 的突变或功能障碍可导致疾病。越来越多的证据表明 LONP1 与各种人类疾病有关，如肿瘤、神经退行性疾病和心脏病。本文综述了 LONP1 的发现、分子结构、亚细胞定位、组织分布和线粒体功能。此外，总结了 LONP1 与肿瘤、神经退行性疾病和心脏病之间的关联，探讨了其在不同疾病中的作用和潜在分子机制。还分析了相关抑制剂和激动剂对 LONP1 的调节作用。鉴于 LONP1 的多效性，对 LONP1 的研究对于理解相关病理生理过程以及制定调节和控制这些相关疾病的策略至关重要。
