Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
Research Programs Unit, Stem Cells and Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
J Clin Invest. 2020 Jan 2;130(1):20-28. doi: 10.1172/JCI129202.
High-throughput technologies for genomics, transcriptomics, proteomics, and metabolomics, and integrative analysis of these data, enable new, systems-level insights into disease pathogenesis. Mitochondrial diseases are an excellent target for hypothesis-generating omics approaches, as the disease group is mechanistically exceptionally complex. Although the genetic background in mitochondrial diseases is in either the nuclear or the mitochondrial genome, the typical downstream effect is dysfunction of the mitochondrial respiratory chain. However, the clinical manifestations show unprecedented variability, including either systemic or tissue-specific effects across multiple organ systems, with mild to severe symptoms, and occurring at any age. So far, the omics approaches have provided mechanistic understanding of tissue-specificity and potential treatment options for mitochondrial diseases, such as metabolome remodeling. However, no curative treatments exist, suggesting that novel approaches are needed. In this Review, we discuss omics approaches and discoveries with the potential to elucidate mechanisms of and therapies for mitochondrial diseases.
高通量技术可用于基因组学、转录组学、蛋白质组学和代谢组学，并对这些数据进行综合分析，从而为疾病发病机制提供新的系统层面的见解。线粒体疾病是生成假设的组学方法的绝佳目标，因为疾病组在机制上异常复杂。尽管线粒体疾病的遗传背景存在于核基因组或线粒体基因组中，但典型的下游效应是线粒体呼吸链功能障碍。然而，临床表现表现出前所未有的可变性，包括跨越多个器官系统的全身或组织特异性影响，症状从轻度到重度，发生在任何年龄。到目前为止，组学方法已经为线粒体疾病的组织特异性和潜在治疗选择提供了机制理解，例如代谢组重塑。然而，目前还没有治愈方法，这表明需要新的方法。在这篇综述中，我们讨论了具有阐明线粒体疾病机制和治疗方法潜力的组学方法和发现。
