线粒体疾病是一类由线粒体DNA或核DNA突变引起的高度异质性遗传病，其临床表现复杂且诊断困难。随着高通量测序技术的发展，多组学技术已成为解析此类疾病分子机制、提升临床诊疗水平的关键手段。本文以典型的线粒体疾病为切入点，综述了基因组学、转录组学、蛋白质组学、代谢组学以及单细胞测序技术等多组学技术在解析线粒体疾病遗传和表型异质性难题、阐明细胞/组织特异性机制方面的研究进展，旨在为多组学技术在线粒体医学领域中从基础研究到临床应用的转化提供借鉴和参考。

Mitochondrial diseases are a group of highly heterogeneous genetic disorders that affect any organ at any age, caused by mutations in nuclear and mitochondrial genes, characterized by complex clinical manifestations and diagnostic challenges. Multi-omics technologies have emerged as essential tools for deciphering the molecular basis of these diseases and improving clinical outcomes. This review summarizes the research progress of multi-omics approaches—including genomics, transcriptomics, proteomics, metabolomics, and single-cell sequencing—in resolving genetic and phenotypic heterogeneity and elucidating cell- and tissue-specific mechanisms of representative mitochondrial diseases. We aim to provide a reference and framework for the translation of multi-omics technologies from basic research to clinical application within the field of mitochondrial medicine.