In this study, combined genome, transcriptome, and metabolome analysis was performed for eight Saccharomyces cerevisiae mitochondrial respiration-deficient mutants. Each mutant exhibited a unique nuclear genome mutation pattern; the nuclear genome mutations, and thus potentially affected genes and metabolic pathways, showed a co-occurrence frequency of ≤ 3 among the eight mutants. For example, only a lipid metabolism-related pathway was likely to be affected by the nuclear genome mutations in one of the mutants. However, large deletions in the mitochondrial genome were the shared characteristic among the eight mutants. At the transcriptomic level, lipid metabolism was the most significantly enriched Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway for differentially expressed genes (DEGs) co-occurring in both ≥ 4 and ≥ 5 mutants. Any identified DEG enriched in lipid metabolism showed the same up-/down-regulated pattern among nearly all eight mutants. Further, 126 differentially expressed lipid species (DELS) were identified, which also showed the same up-/down-regulated pattern among nearly all investigated mutants. It was conservatively demonstrated that the similar change pattern of lipid metabolism in the entire investigated mutant population was attributed to mitochondrial dysfunction. The change spectrum of lipid species was presented, suggesting that the number and change degree of up-regulated lipid species were higher than those of down-regulated lipid species. Additionally, energy storage lipids increased in content and plasma-membrane phospholipid compositions varied in the relative proposition. The results for the genome, transcriptome, and lipidome were mutually validated, which provides quantitative data revealing the roles of mitochondria from a global cellular perspective.

中文翻译：

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线粒体功能障碍对酿酒酵母脂质代谢影响的定量多组学分析。

在这项研究中，对八个酿酒酵母线粒体呼吸缺陷型突变体进行了基因组，转录组和代谢组学分析。每个突变体表现出独特的核基因组突变模式。八个突变体中，核基因组突变以及因此可能受影响的基因和代谢途径的共现频率≤3。例如，在一个突变体中，只有脂质代谢相关途径才可能受到核基因组突变的影响。然而，线粒体基因组中的大缺失是八个突变体之间的共同特征。在转录组水平上，对于≥4和≥5突变体中同时存在的差异表达基因（DEG），脂质代谢是最丰富的京都基因和基因组百科全书（KEGG）途径。在几乎所有八个突变体中，任何鉴定出的富含脂质代谢的DEG都显示出相同的上/下调模式。此外，鉴定了126种差异表达的脂质种类（DELS），在几乎所有研究的突变体中也显示出相同的上/下调模式。保守地证明，在整个研究的突变人群中脂质代谢的相似变化模式归因于线粒体功能障碍。给出了脂质种类的变化谱，表明上调脂质种类的数量和变化程度高于下调脂质种类。另外，储能脂质的含量增加，并且血浆膜磷脂的组成在相对位置上变化。基因组，转录组，