Xu Jie, Wei Huanglong, Sun Zhenyu, Li Wankang, Long Jiangang, Liu Jiankang, Feng Zhihui, Cao Ke
Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao 266071, China.
Antioxidants (Basel). 2025 Mar 27;14(4):398. doi: 10.3390/antiox14040398.
Hydroxytyrosol (HT), a principal bioactive phytochemical abundant in Mediterranean dietary sources, has emerged as a molecule of significant scientific interest owing to its multifaceted health-promoting properties. Accumulating evidence suggests that HT's therapeutic potential in metabolic disorders extends beyond conventional antioxidant capacity to encompass mitochondrial regulatory networks. This review synthesizes contemporary evidence from our systematic investigations and the existing literature to delineate HT's comprehensive modulatory effects on mitochondrial homeostasis. We systematically summarized the impact of HT on mitochondrial dynamics (fusion/fission equilibrium), biogenesis and energy metabolism, mitophagy, inter-organellar communication with the endoplasmic reticulum, and microbiota-mitochondria crosstalk. Through this multidimensional analysis, we established HT as a mitochondrial homeostasis modulator with potential therapeutic applications in metabolic syndrome (MetS) and its related pathologies including type 2 diabetes mellitus, obesity-related metabolic dysfunction, dyslipidemia, non-alcoholic steatohepatitis, and hypertension-related complications. Moreover, we further discussed translational challenges in HT research, emphasizing the imperative for direct target identification, mitochondrial-targeted delivery system development, and combinatorial therapeutic strategies. Collectively, this review provides a mechanistic framework for advancing HT research and accelerating its clinical implementation in MetS and its related diseases.
羟基酪醇（HT）是地中海饮食来源中丰富的一种主要生物活性植物化学物质，由于其多方面的健康促进特性，已成为具有重大科学意义的分子。越来越多的证据表明，HT在代谢紊乱中的治疗潜力不仅限于传统的抗氧化能力，还包括线粒体调节网络。本综述综合了我们系统研究和现有文献中的当代证据，以描述HT对线粒体稳态的全面调节作用。我们系统地总结了HT对线粒体动力学（融合/裂变平衡）、生物发生和能量代谢、线粒体自噬、与内质网的细胞器间通讯以及微生物群-线粒体相互作用的影响。通过这种多维度分析，我们确定HT是一种线粒体稳态调节剂，在代谢综合征（MetS）及其相关病理包括2型糖尿病、肥胖相关代谢功能障碍、血脂异常、非酒精性脂肪性肝炎和高血压相关并发症中具有潜在的治疗应用。此外，我们进一步讨论了HT研究中的转化挑战，强调了直接靶点识别、线粒体靶向递送系统开发和联合治疗策略的必要性。总体而言，本综述为推进HT研究以及加速其在MetS及其相关疾病中的临床应用提供了一个机制框架。
