胆固醇通过调节膜层的结构和功能性质，是膜层双层中不可或缺的组成部分。胆固醇通过运输到包括线粒体在内的不同细胞区域中，其胆固醇含量与其他细胞膜相比较低。尽管在内线粒体膜（IMM）中胆固醇的可用性有限，但胆固醇在IMM中的代谢在生理作用中起着重要的作用，作为合成甾体激素和神经甾体激素的前体，在甾体激素组织和特定神经元中发挥作用，或通过肝脏中的另一条途径合成胆汁酸。线粒体中的胆固醇积累超出了生理水平会通过多种机制对线粒体功能产生负面影响，包括限制关键抗氧化防御（如谷胱甘肽还原循环），增加反应性氧化物质的生成和随后的磷脂酰肌醇的氧化修饰以及呼吸超复合物的缺陷组装等。增加线粒体胆固醇运输的这些有害后果会引发氧化应激和细胞死亡，最终导致不同疾病（包括代谢性肝病（如脂肪肝和肝癌），溶酶体疾病（如尼曼-匹克C型疾病）和神经退行性疾病（如阿尔茨海默病））的发展。在本综述中，我们概述线粒体胆固醇的代谢和调节以及其对肝脏和神经退行性疾病的潜在影响。版权所有©2023作者。由Elsevier B.V.出版保留所有权利。

Cholesterol is a crucial component of membrane bilayers by regulating their structural and functional properties. Cholesterol traffics to different cellular compartments including mitochondria, whose cholesterol content is low compared to other cell membranes. Despite the limited availability of cholesterol in the inner mitochondrial membrane (IMM), the metabolism of cholesterol in the IMM plays important physiological roles, acting as the precursor for the synthesis of steroid hormones and neurosteroids in steroidogenic tissues and specific neurons, respectively, or the synthesis of bile acids through an alternative pathway in the liver. Accumulation of cholesterol in mitochondria above physiological levels has a negative impact on mitochondrial function through several mechanisms, including the limitation of crucial antioxidant defenses, such as the glutathione redox cycle, increased generation of reactive oxygen species and consequent oxidative modification of cardiolipin, and defective assembly of respiratory supercomplexes. These adverse consequences of increased mitochondrial cholesterol trafficking trigger the onset of oxidative stress and cell death, and, ultimately, contribute to the development of diverse diseases, including metabolic liver diseases (i.e. fatty liver disease and liver cancer), as well as lysosomal disorders (i.e. Niemann-Pick type C disease) and neurodegenerative diseases (i.e. Alzheimer's disease). In this review, we summarize the metabolism and regulation of mitochondrial cholesterol and its potential impact on liver and neurodegenerative diseases.Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.