Superoxide dismutase 1 (SOD1) has conventionally been recognized as a classical antioxidant enzyme, safeguarding cells against oxidative stress. However, recent studies have unveiled novel noncanonical functions of SOD1, challenging its traditional role solely as an antioxidant enzyme. Despite this progress, there remains a dearth of research elucidating direct molecular mechanisms and metabolic implications of these non-enzymatic functions. This dissertation aimed to address this gap by investigating the protein-protein interactions (PPIs) of SOD1 and their roles in cellular metabolism.The methodology employed in this study encompassed the identification of SOD1 interactors using cross-linking immunoprecipitation mass spectrometry (XIP-MS) assays, followed by the validation of these interactions through protein complementary assays (PCA) and co-immunoprecipitation (Co-IP) techniques. Subsequently, this research endeavored to elucidate the molecular mechanisms and metabolic ramifications stemming from these PPIs. The overarching objectives of this dissertation were to identify PPIs and shared characteristics between SOD1 and two activation proteins, YWHAE and YWHAZ, as well as two elongation factors, EEF1A1 and EEFSEC. Additionally, by unraveling the molecular underpinnings governing the metabolic functions of these PPIs in lipid metabolism, cell growth, protein synthesis, and selenoprotein metabolism, our aim was to unveil new biomarkers and therapeutic strategies to address previously inexplicable SOD1-related metabolic disorders and pathologies, as outlined in Chapter 2. In Chapter 3, the study aimed to uncover new molecular mechanisms underlying disordered lipid metabolism in SOD1-deficient mice, where abnormal hepatic lipid deposition could not be solely attributed to redox imbalance from our previous finding. Notably, the PPIs between SOD1 and YWHAE or YWHAZ were found to regulate lipid metabolism, along with novel roles in cell growth, by augmenting SOD1 stability and activity, thereby influencing gene expression levels in lipolysis and cell cycle pathways. Chapter 4 focused on exploring the novel functional roles of SOD1 in protein translation through its interactions with EEF1A1 and EEFSEC. These PPIs were found to enhance the elongation rate during protein synthesis and selenocysteine incorporation rate during selenoprotein synthesis, respectively. Consequently, SOD1 deficiency in mice was found to impact in vivo de novo protein synthesis and selenoproteins metabolism as metabolic implications. Overall, this study provides valuable insights into the multifaceted roles of SOD1 in cellular metabolism and highlights the significance of protein-protein interactions in governing metabolic processes. 超氧化物歧化酶1（SOD1）传统上被认为是一种经典的抗氧化酶，能够保护细胞免受氧化应激的侵害。然而，最近的研究揭示了SOD1的新型非经典功能，挑战了其单纯作为抗氧化酶的传统角色。尽管取得了这一进展，但仍然缺乏关于这些非酶功能的直接分子机制和代谢影响的研究。本论文旨在通过研究SOD1的蛋白质相互作用（PPIs）及其在细胞代谢中的作用来填补这一空白。本研究采用的方法包括使用交联免疫沉淀质谱（XIP-MS）实验鉴定SOD1的相互作用蛋白，然后通过蛋白互补（PCA）和共免疫沉淀（Co-IP）技术验证这些相互作用。随后，本研究致力于阐明这些PPIs所引起的分子机制和代谢后果。 本论文的主要目标是识别SOD1与两种激活蛋白YWHAE和YWHAZ以及两种延伸因子EEF1A1和EEFSEC之间的PPIs和共同特征。此外，通过揭示这些PPIs在脂质代谢、细胞生长、蛋白质合成和硒蛋白代谢等代谢功能中的分子基础，我们的目标是揭示新的生物标志物和治疗策略，以解决先前无法解释的与SOD1相关的代谢障碍和病理学问题，如第二章所述。 在第三章中，本研究旨在揭示SOD1缺乏小鼠中脂质代谢紊乱的新的分子机制，其中异常的肝脂沉积不能单纯归因于我们先前发现的氧化还原失衡。值得注意的是，SOD1与YWHAE或YWHAZ之间的PPIs被发现能够调节脂质代谢，以及对细胞生长的新角色，通过增强SOD1的稳定性和活性，从而影响脂解和细胞周期通路中的基因表达水平。 第四章重点研究了SOD1在蛋白质翻译中的新功能角色，通过其与EEF1A1和EEFSEC的相互作用。这些PPIs被发现能够增强蛋白质合成过程中的延伸速率，以及硒蛋白合成过程中的硒氨酸结合速率。因此，SOD1在小鼠中的缺乏被发现影响体内新的蛋白质合成和硒蛋白代谢作为代谢影响。 总的来说，本研究为我们深入了解SOD1在细胞代谢中的多方面作用提供了宝贵的见解，并强调了蛋白质相互作用在调节代谢过程中的重要性。