Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Comprehensive Alcohol-HIV/AIDS Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Int J Mol Sci. 2023 May 12;24(10):8650. doi: 10.3390/ijms24108650.
Alcohol misuse, directly or indirectly as a result of its metabolism, negatively impacts most tissues, including four with critical roles in energy metabolism regulation: the liver, pancreas, adipose, and skeletal muscle. Mitochondria have long been studied for their biosynthetic roles, such as ATP synthesis and initiation of apoptosis. However, current research has provided evidence that mitochondria participate in myriad cellular processes, including immune activation, nutrient sensing in pancreatic β-cells, and skeletal muscle stem and progenitor cell differentiation. The literature indicates that alcohol impairs mitochondrial respiratory capacity, promoting reactive oxygen species (ROS) generation and disrupting mitochondrial dynamics, leading to dysfunctional mitochondria accumulation. As discussed in this review, mitochondrial dyshomeostasis emerges at a nexus between alcohol-disrupted cellular energy metabolism and tissue injury. Here, we highlight this link and focus on alcohol-mediated disruption of immunometabolism, which refers to two distinct, yet interrelated processes. Extrinsic immunometabolism involves processes whereby immune cells and their products influence cellular and/or tissue metabolism. Intrinsic immunometabolism describes immune cell fuel utilization and bioenergetics that affect intracellular processes. Alcohol-induced mitochondrial dysregulation negatively impacts immunometabolism in immune cells, contributing to tissue injury. This review will present the current state of literature, describing alcohol-mediated metabolic and immunometabolic dysregulation from a mitochondrial perspective.
酗酒，无论是直接还是间接通过其代谢产物，都会对大多数组织造成负面影响，包括在能量代谢调节中起关键作用的四个组织：肝脏、胰腺、脂肪组织和骨骼肌。线粒体的生物合成作用（如 ATP 合成和凋亡起始）一直是研究的热点。然而，目前的研究已经提供了证据表明，线粒体参与了许多细胞过程，包括免疫激活、胰腺 β 细胞中的营养感应以及骨骼肌干细胞和祖细胞的分化。文献表明，酒精会损害线粒体呼吸能力，促进活性氧（ROS）的产生并破坏线粒体动态平衡，导致功能失调的线粒体积累。正如本综述中所讨论的，线粒体功能障碍出现在酒精破坏细胞能量代谢和组织损伤的交汇点。在这里，我们强调这一联系，并重点关注酒精介导的免疫代谢紊乱，这是指两个不同但相互关联的过程。外在免疫代谢涉及免疫细胞及其产物影响细胞和/或组织代谢的过程。内在免疫代谢描述了影响细胞内过程的免疫细胞燃料利用和生物能学。酒精引起的线粒体失调会对免疫细胞的免疫代谢产生负面影响，从而导致组织损伤。本综述将呈现目前的文献状态，从线粒体的角度描述酒精介导的代谢和免疫代谢紊乱。
