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Abstract：
Glioblastoma, a type of cancer affecting the central nervous system, is characterized by its poor prognosis and the dynamic alteration of its metabolic phenotype to fuel development and progression. Critical to cellular metabolism, mitochondria play a pivotal role, where the acetylation of lysine residues on mitochondrial enzymes emerges as a crucial regulatory mechanism of protein function. This post-translational modification, which negatively impacts the mitochondrial proteome\'s functionality, is modulated by the enzyme sirtuin 3 (SIRT3). Aiming to elucidate the regulatory role of SIRT3 in mitochondrial metabolism within glioblastoma, we employed high-resolution mass spectrometry to analyze the proteome and acetylome of two glioblastoma cell lines, each exhibiting distinct metabolic behaviors, following the chemical inhibition of SIRT3. Our findings reveal that the protein synthesis machinery, regulated by lysine acetylation, significantly influences the metabolic phenotype of these cells. Moreover, we have shed light on potential novel SIRT3 targets, thereby unveiling new avenues for future investigations. This research highlights the critical function of SIRT3 in mitochondrial metabolism and its broader implications for cellular energetics. It also provides a comparative analysis of the proteome and acetylome across glioblastoma cell lines with opposing metabolic phenotypes.
摘要：
胶质母细胞瘤,一种影响中枢神经系统的癌症，其特征在于其预后不良以及其代谢表型对燃料发育和进展的动态改变。对细胞新陈代谢至关重要，线粒体起着举足轻重的作用,其中线粒体酶上赖氨酸残基的乙酰化成为蛋白质功能的关键调节机制。这种翻译后修饰，对线粒体蛋白质组的功能产生负面影响，由酶沉默酶3(SIRT3)调节。旨在阐明SIRT3在胶质母细胞瘤线粒体代谢中的调节作用，我们采用高分辨率质谱分析两种胶质母细胞瘤细胞系的蛋白质组和乙酰组，每个都表现出不同的代谢行为，在SIRT3的化学抑制之后。我们的发现揭示了蛋白质合成机制，由赖氨酸乙酰化调节，显著影响这些细胞的代谢表型。此外，我们已经揭示了潜在的新型SIRT3目标，从而为未来的调查开辟了新的途径。这项研究强调了SIRT3在线粒体代谢中的关键功能及其对细胞能量学的更广泛意义。它还提供了对具有相反代谢表型的成胶质细胞瘤细胞系的蛋白质组和乙酰组的比较分析。
