Department of Internal Medicine, School of Medicine, Kyungpook National University Chilgok Hospital, Daegu 41404, Korea.
Research Institute of Aging and Metabolism, Kyungpook National University, Daegu 41566, Korea.
Mol Cells. 2023 May 31;46(5):259-267. doi: 10.14348/molcells.2023.2128. Epub 2023 Feb 9.
Pyruvate metabolism, a key pathway in glycolysis and oxidative phosphorylation, is crucial for energy homeostasis and mitochondrial quality control (MQC), including fusion/fission dynamics and mitophagy. Alterations in pyruvate flux and MQC are associated with reactive oxygen species accumulation and Ca flux into the mitochondria, which can induce mitochondrial ultrastructural changes, mitochondrial dysfunction and metabolic dysregulation. Perturbations in MQC are emerging as a central mechanism for the pathogenesis of various metabolic diseases, such as neurodegenerative diseases, diabetes and insulin resistance-related diseases. Mitochondrial Ca regulates the pyruvate dehydrogenase complex (PDC), which is central to pyruvate metabolism, by promoting its dephosphorylation. Increase of pyruvate dehydrogenase kinase (PDK) is associated with perturbation of mitochondria-associated membranes (MAMs) function and Ca flux. Pyruvate metabolism also plays an important role in immune cell activation and function, dysregulation of which also leads to insulin resistance and inflammatory disease. Pyruvate metabolism affects macrophage polarization, mitochondrial dynamics and MAM formation, which are critical in determining macrophage function and immune response. MAMs and MQCs have also been intensively studied in macrophage and T cell immunity. Metabolic reprogramming connected with pyruvate metabolism, mitochondrial dynamics and MAM formation are important to macrophages polarization (M1/M2) and function. T cell differentiation is also directly linked to pyruvate metabolism, with inhibition of pyruvate oxidation by PDKs promoting proinflammatory T cell polarization. This article provides a brief review on the emerging role of pyruvate metabolism in MQC and MAM function, and how dysfunction in these processes leads to metabolic and inflammatory diseases.
丙酮酸代谢是糖酵解和氧化磷酸化的关键途径，对能量平衡和线粒体质量控制（MQC）至关重要，包括融合/裂变动力学和线粒体自噬。丙酮酸通量和 MQC 的改变与活性氧物质的积累和 Ca 流入线粒体有关，这可能导致线粒体超微结构的改变、线粒体功能障碍和代谢失调。MQC 的紊乱正在成为各种代谢疾病发病机制的一个核心机制，如神经退行性疾病、糖尿病和与胰岛素抵抗相关的疾病。线粒体 Ca 通过促进其去磷酸化来调节丙酮酸脱氢酶复合物（PDC），PDC 是丙酮酸代谢的核心。丙酮酸脱氢酶激酶（PDK）的增加与线粒体相关膜（MAMs）功能和 Ca 流的紊乱有关。丙酮酸代谢在免疫细胞的激活和功能中也起着重要作用，其失调也会导致胰岛素抵抗和炎症性疾病。丙酮酸代谢影响巨噬细胞极化、线粒体动力学和 MAM 的形成，这对于确定巨噬细胞的功能和免疫反应至关重要。MAMs 和 MQCs 在巨噬细胞和 T 细胞免疫中也得到了深入研究。与丙酮酸代谢、线粒体动力学和 MAM 形成相关的代谢重编程对于巨噬细胞极化（M1/M2）和功能很重要。T 细胞分化也与丙酮酸代谢直接相关，PDKs 抑制丙酮酸氧化促进了促炎 T 细胞的极化。本文简要综述了丙酮酸代谢在 MQC 和 MAM 功能中的新作用，以及这些过程的功能障碍如何导致代谢和炎症性疾病。
