线粒体,真核细胞能量的主要提供者,含有1000多种不同的蛋白质,与细胞发育密切相关。然而,受损的蛋白质损害线粒体功能,进一步导致多种人类疾病。证据表明线粒体蛋白酶对于蛋白质维持至关重要。最重要的是,质量控制酶通过降解错误折叠在调节线粒体功能中发挥关键作用,年龄,或者多余的蛋白质.有趣的是,癌细胞在破坏蛋白质的压力条件下茁壮成长,因此,靶向线粒体质量控制蛋白酶可作为癌细胞的新型调节剂。不仅如此,线粒体质量控制蛋白酶已被证明通过调节视神经萎缩1(OPA1)的形态来影响线粒体动力学,与癌症的发生、发展密切相关。在这次审查中,我们引入线粒体质量控制蛋白酶作为癌症治疗中的有希望的靶标和相关调节剂,重点是酪蛋白分解蛋白酶P(ClpP),Lon蛋白酶(LonP1),高温需求蛋白A2(HrtA2),OMA-1Further,我们总结了我们目前对线粒体质控蛋白酶调节剂临床试验进展的认识.总的来说,上述内容为新型抗肿瘤药物的开发提供了方向。
Mitochondria, the main provider of energy in eukaryotic cells, contains more than 1000 different proteins and is closely related to the development of cells. However, damaged proteins impair mitochondrial function, further contributing to several human diseases. Evidence shows mitochondrial proteases are critically important for protein maintenance. Most importantly, quality control enzymes exert a crucial role in the modulation of mitochondrial functions by degrading misfolded, aged, or superfluous proteins. Interestingly, cancer cells thrive under stress conditions that damage proteins, so targeting mitochondrial quality control proteases serves as a novel regulator for cancer cells. Not only that, mitochondrial quality control proteases have been shown to affect mitochondrial dynamics by regulating the morphology of optic atrophy 1 (OPA1), which is closely related to the occurrence and progression of cancer. In this review, we introduce mitochondrial quality control proteases as promising targets and related modulators in cancer therapy with a focus on caseinolytic protease P (ClpP), Lon protease (LonP1), high-temperature requirement protein A2 (HrtA2), and OMA-1. Further, we summarize our current knowledge of the advances in clinical trials for modulators of mitochondrial quality control proteases. Overall, the content proposed above serves to suggest directions for the development of novel antitumor drugs.