In addition to oxidative phosphorylation (OXPHOS), mitochondria perform other functions such as heme biosynthesis and oxygen sensing and mediate calcium homeostasis, cell growth, and cell death. They participate in cell communication and regulation of inflammation and are important considerations in aging, drug toxicity, and pathogenesis. The cell's capacity to maintain its mitochondria involves intramitochondrial processes, such as heme and protein turnover, and those involving entire organelles, such as fusion, fission, selective mitochondrial macroautophagy (mitophagy), and mitochondrial biogenesis. The integration of these processes exemplifies mitochondrial quality control (QC), which is also important in cellular disorders ranging from primary mitochondrial genetic diseases to those that involve mitochondria secondarily, such as neurodegenerative, cardiovascular, inflammatory, and metabolic syndromes. Consequently, mitochondrial biology represents a potentially useful, but relatively unexploited area of therapeutic innovation. In patients with genetic OXPHOS disorders, the largest group of inborn errors of metabolism, effective therapies, apart from symptomatic and nutritional measures, are largely lacking. Moreover, the genetic and biochemical heterogeneity of these states is remarkably similar to those of certain acquired diseases characterized by metabolic and oxidative stress and displaying wide variability. This biologic variability reflects cell-specific and repair processes that complicate rational pharmacological approaches to both primary and secondary mitochondrial disorders. However, emerging concepts of mitochondrial turnover and dynamics along with new mitochondrial disease models are providing opportunities to develop and evaluate mitochondrial QC-based therapies. The goals of such therapies extend beyond amelioration of energy insufficiency and tissue loss and entail cell repair, cell replacement, and the prevention of fibrosis. This review summarizes current concepts of mitochondria as disease elements and outlines novel strategies to address mitochondrial dysfunction through the stimulation of mitochondrial biogenesis and quality control.

中文翻译：

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线粒体质量控制作为治疗目标。


除了氧化磷酸化 (OXPHOS) 之外，线粒体还执行其他功能，例如血红素生物合成和氧传感，并介导钙稳态、细胞生长和细胞死亡。它们参与细胞通讯和炎症调节，是衰老、药物毒性和发病机制的重要考虑因素。细胞维持线粒体的能力涉及线粒体内过程，例如血红素和蛋白质周转，以及涉及整个细胞器的过程，例如融合、裂变、选择性线粒体自噬（线粒体自噬）和线粒体生物发生。这些过程的整合体现了线粒体质量控制（QC），这在细胞疾病中也很重要，从原发性线粒体遗传病到继发性涉及线粒体的疾病，如神经退行性、心血管、炎症和代谢综合征。因此，线粒体生物学代表了一个潜在有用但相对尚未开发的治疗创新领域。遗传性 OXPHOS 疾病是最大的先天性代谢缺陷群体，对于患有遗传性 OXPHOS 疾病的患者，除了对症和营养措施外，很大程度上缺乏有效的治疗方法。此外，这些状态的遗传和生化异质性与某些以代谢和氧化应激为特征并表现出广泛变异性的获得性疾病的异质性非常相似。这种生物变异性反映了细胞特异性和修复过程，使原发性和继发性线粒体疾病的合理药理学方法变得复杂。 然而，线粒体周转和动力学的新兴概念以及新的线粒体疾病模型为开发和评估基于线粒体 QC 的疗法提供了机会。此类疗法的目标不仅限于改善能量不足和组织损失，还包括细胞修复、细胞替代和预防纤维化。这篇综述总结了线粒体作为疾病要素的当前概念，并概述了通过刺激线粒体生物发生和质量控制来解决线粒体功能障碍的新策略。