Pareek Jyotsna, Mudgal Pallavi, Sindhu Nitika, Tiwari Vaibhav, Tripathi Dinesh Mani, Paliwal Swati
Department of Bioscience and Biotechnology, Banasthali Vidyapith, Tonk, Rajasthan, 304022, India.
Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences (ILBS), Vasant Kunj, New Delhi, 110070, India.
Cell Tissue Res. 2025 May 26. doi: 10.1007/s00441-025-03977-z.
Mitochondria transplantation is an emerging therapeutic strategy with remarkable potential in treating various diseases associated with mitochondrial dysfunction. Despite the known differences in tissue-specific mitochondria, the therapeutic outcomes of mitochondria isolated from various sources, after their transplantation in a specific disease model has remained elusive. In this study, we investigated the tissue-dependent therapeutic differences after transplantation of mitochondria isolated from heart, muscle, and liver tissues in a high-fat diet and streptozotocin, 35 mg/Kg (HFD + STZ) induced metabolic syndrome (MetS) in Wistar rats. We found striking differences in lowering of blood glucose levels, blood pressure, cholesterol, ALT, and AST levels in MetS after transplantation of mitochondria obtained from heart, muscle, and liver tissues (P < 0.01). Liver mitochondria transplantation demonstrated the most effective upregulation of mitochondrial complex activities, enhanced anti-oxidant enzyme levels in recipient liver tissues (P < 0.01). It also upregulated gene expression of genes associated with mitochondrial biogenesis and bioenergetics and reduced apoptosis and inflammation associated genes in HFD + STZ rats. In addition, GC-MS metabolite analysis revealed differential blood serum concentrations of key tri-carboxylic acid metabolites such as succinic acid, malic acid, alpha-ketoglutarate, citric acid, and pyruvate after mitochondrial transplantation in HFD + STZ rats. This study supports the idea that mitochondria source tissue should be considered to provide better clinical outcomes for mitochondrial transplantation.
线粒体移植是一种新兴的治疗策略，在治疗各种与线粒体功能障碍相关的疾病方面具有巨大潜力。尽管已知组织特异性线粒体存在差异，但从各种来源分离的线粒体在特定疾病模型中移植后的治疗效果仍不明确。在本研究中，我们调查了将从心脏、肌肉和肝脏组织分离的线粒体移植到高脂饮食和35 mg/Kg链脲佐菌素（HFD + STZ）诱导的Wistar大鼠代谢综合征（MetS）模型后，组织依赖性的治疗差异。我们发现，移植从心脏、肌肉和肝脏组织获得的线粒体后，MetS大鼠的血糖水平、血压、胆固醇、谷丙转氨酶（ALT）和谷草转氨酶（AST）水平降低存在显著差异（P < 0.01）。肝脏线粒体移植显示出线粒体复合物活性的最有效上调，受体肝脏组织中的抗氧化酶水平增强（P < 0.01）。它还上调了与线粒体生物发生和生物能量学相关基因的表达，并降低了HFD + STZ大鼠中与细胞凋亡和炎症相关的基因表达。此外，气相色谱-质谱（GC-MS）代谢物分析显示，在HFD + STZ大鼠中进行线粒体移植后，血清中琥珀酸、苹果酸、α-酮戊二酸、柠檬酸和丙酮酸等关键三羧酸代谢物的浓度存在差异。这项研究支持这样一种观点，即应考虑线粒体来源组织，以为线粒体移植提供更好的临床结果。
