Cholesterol is a crucial component of membrane bilayers that determines their physical and functional properties. Cells largely satisfy their need for cholesterol through the novo synthesis from acetyl-CoA and this demand is particularly critical for cancer cells to sustain dysregulated cell proliferation. However, the association between serum or tissue cholesterol levels and cancer development is not well established as epidemiologic data do not consistently support this link. While most preclinical studies focused on the role of total celular cholesterol, the specific contribution of the mitochondrial cholesterol pool to alterations in cancer cell biology has been less explored. Although low compared to other bilayers, the mitochondrial cholesterol content plays an important physiological function in the synthesis of steroid hormones in steroidogenic tissues or bile acids in the liver and controls mitochondrial function. In addition, mitochondrial cholesterol metabolism generates oxysterols, which in turn, regulate multiple pathways, including cholesterol and lipid metabolism as well as cell proliferation. In the present review, we summarize the regulation of mitochondrial cholesterol, including its role in mitochondrial routine performance, cell death and chemotherapy resistance, highlighting its potential contribution to cancer. Of particular relevance is hepatocellular carcinoma, whose incidence in Western countries had tripled in the past decades due to the obesity and type II diabetes epidemic. A better understanding of the role of mitochondrial cholesterol in cancer development may open up novel opportunities for cancer therapy.

胆固醇是膜双层的重要组成部分，决定其物理和功能特性。细胞通过乙酰辅酶A的新合成很大程度上满足了对胆固醇的需求，这种需求对于癌细胞维持失调的细胞增殖尤其重要。然而，血清或组织胆固醇水平与癌症发展之间的关联尚未明确，因为流行病学数据并不一致支持这种联系。虽然大多数临床前研究都集中在细胞总胆固醇的作用上，但线粒体胆固醇库对癌细胞生物学改变的具体贡献却鲜有探讨。虽然与其他双层相比较低，但线粒体胆固醇含量在类固醇生成组织中的类固醇激素或肝脏中胆汁酸的合成中发挥着重要的生理功能，并控制线粒体功能。此外，线粒体胆固醇代谢产生氧甾醇，氧甾醇反过来调节多种途径，包括胆固醇和脂质代谢以及细胞增殖。在本综述中，我们总结了线粒体胆固醇的调节，包括其在线粒体常规性能、细胞死亡和化疗耐药中的作用，强调了其对癌症的潜在贡献。特别相关的是肝细胞癌，由于肥胖和二型糖尿病的流行，过去几十年来西方国家的肝细胞癌发病率增加了两倍。更好地了解线粒体胆固醇在癌症发展中的作用可能会为癌症治疗开辟新的机会。