Department of Biomedicine & Health Sciences, The Catholic University of Korea, 222 Banpo‑daero, Seocho‑ku, Seoul, 065‑591, Republic of Korea.
Department of Medical Life Sciences, The Catholic University of Korea, 222 Banpo‑daero, Seocho‑ku, Seoul, 065‑591, Republic of Korea.
Genes Genomics. 2023 Mar;45(3):261-270. doi: 10.1007/s13258-022-01359-1. Epub 2023 Jan 7.
Mitochondria are organelles that serve as a central hub for physiological processes in eukaryotes, including production of ATP, regulation of calcium dependent signaling, generation of ROS, and regulation of apoptosis. Cancer cells undergo metabolic reprogramming in an effort to support their increasing requirements for cell survival, growth, and proliferation, and mitochondria have primary roles in these processes. Because of their central function in survival of cancer cells and drug resistance, mitochondria are an important target in cancer therapy and many drugs targeting mitochondria that target the TCA cycle, apoptosis, metabolic pathway, and generation of ROS have been developed. Continued use of mitochondrial-targeting drugs can lead to resistance due to development of new somatic mutations. Use of drugs is limited due to these mutations, which have been detected in mitochondrial proteins. In this review, we will focus on genetic mutations in mitochondrial target proteins and their function in induction of drug-resistance.
线粒体是真核生物生理过程的中心枢纽，包括 ATP 的生成、钙依赖性信号的调节、ROS 的产生和细胞凋亡的调节。癌细胞为了支持其不断增加的细胞存活、生长和增殖的需求，经历了代谢重编程，线粒体在这些过程中起着主要作用。由于线粒体在癌细胞存活和耐药性方面的核心作用，线粒体是癌症治疗的一个重要靶点，许多针对线粒体的药物已经被开发出来，这些药物靶向 TCA 循环、细胞凋亡、代谢途径和 ROS 的产生。由于新的体细胞突变的出现，持续使用线粒体靶向药物会导致耐药性。由于这些突变已经在线粒体蛋白中被检测到，因此药物的使用受到限制。在这篇综述中，我们将重点关注线粒体靶蛋白的遗传突变及其在诱导耐药性中的作用。
