Vice presidency for Scientific Research and Innovation, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
King Abdulaziz and his Companions Foundation for Giftedness and Creativity "Mawhiba", Riyadh, Saudi Arabia.
Endocrine. 2024 Dec;86(3):903-929. doi: 10.1007/s12020-024-03967-1. Epub 2024 Aug 22.
Mitochondria is a subcellular organelle involved in the pathogenesis of cellular stress, immune responses, differentiation, metabolic disorders, aging, and death by regulating process of fission, fusion, mitophagy, and transport. However, an increased interest in mitochondria as powerhouse for ATP production, the mechanisms of mitochondria-mediated cellular dysfunction in response to hormonal interaction remains unknown. Mitochondrial matrix contains chaperones and proteases that regulate intrinsic apoptosis pathway through pro-apoptotic Bcl-2 family's proteins Bax/Bak, and Cyt C release, and induces caspase-dependent and independent cells death. Energy and growth regulators such as thyroid hormones have profound effect on mitochondrial inner membrane protein and lipid compositions, ATP production by regulating oxidative phosphorylation system. Mitochondria contain cholesterol side-chain cleavage enzyme, P450scc, ferredoxin, and ferredoxin reductase providing an essential site for steroid hormones biosynthesis. In line with this, neurohormones such as oxytocin, vasopressin, and melatonin are correlated with mitochondrial integrity, displaying therapeutic implications for inflammatory and immune responses. Melatonin's also displayed protective role against oxidative stress and mitochondrial synthesis of ROS, suggesting a defense mechanism against aging-related diseases. An imbalance in mitochondrial bioenergetics can cause neurodegenerative disorders, cardiovascular diseases, and cancers. Hormone-induced PGC-1α stimulates mitochondrial biogenesis via activation of NRF1 and NRF2, which in turn triggers mtTFA in brown adipose and cardiac myocytes. Mitochondria can be transferred through cells merging, exosome-mediated transfer, and tunneling through nanotubes. By delineating the underlying molecular mechanism of hormonal mitochondrial interaction, this study reviews the dynamics mechanisms of mitochondria and its effects on cellular level, health, diseases, and therapeutic strategies targeting mitochondrial diseases.
线粒体是一种参与细胞应激、免疫反应、分化、代谢紊乱、衰老和死亡的亚细胞细胞器，通过调节分裂、融合、噬线体和运输过程来发挥作用。然而，人们对线粒体作为 ATP 产生的动力工厂的兴趣日益增加，对于激素相互作用引起的线粒体介导的细胞功能障碍的机制仍不清楚。线粒体基质中含有伴侣蛋白和蛋白酶，它们通过促凋亡 Bcl-2 家族蛋白 Bax/Bak 和 Cyt C 的释放来调节内在凋亡途径，并诱导依赖 caspase 和不依赖 caspase 的细胞死亡。能量和生长调节剂，如甲状腺激素，通过调节氧化磷酸化系统，对线粒体内膜蛋白和脂质组成、ATP 产生有深远影响。线粒体含有胆固醇侧链裂解酶、P450scc、铁氧还蛋白和铁氧还蛋白还原酶，为类固醇激素生物合成提供了一个必要的部位。与此一致的是，神经激素如催产素、加压素和褪黑素与线粒体的完整性相关，显示出对炎症和免疫反应的治疗意义。褪黑素还显示出对氧化应激和线粒体 ROS 合成的保护作用，提示其是对抗与衰老相关疾病的防御机制。线粒体生物能的失衡会导致神经退行性疾病、心血管疾病和癌症。激素诱导的 PGC-1α 通过激活 NRF1 和 NRF2 刺激线粒体生物发生，进而在棕色脂肪和心肌细胞中触发 mtTFA。线粒体可以通过细胞融合、外体介导的转移和通过纳米管的隧道转移。通过描绘激素与线粒体相互作用的潜在分子机制，本研究综述了线粒体的动力学机制及其对细胞水平、健康、疾病的影响，以及针对线粒体疾病的治疗策略。
