Department of Biochemistry, Faculty of Life Sciences, University of Central Punjab, Lahore-54590, Pakistan.
Department of Biological Sciences, International Islamic University, Islamabad-44000, Pakistan.
Anticancer Agents Med Chem. 2022;22(11):2048-2062. doi: 10.2174/1871520621666211126090906.
Apoptosis is a programmed cell death that occurs due to the production of several catabolic enzymes. During this process, several morphological and biochemical changes occur in mitochondria, the main organelle in the cell that participates in apoptosis and controls apoptotic pathways. During apoptosis, cytochrome c is released from mitochondria, and different proteins activate caspase cascades that carry out the cell towards the death process. Apoptosis mainly occurs due to p53 protein that allows the abnormal cells to proliferate. Bcl-2 and Bcl-xl are two anti-apoptotic members of the protein family that prevents apoptosis. The membrane potential of mitochondria decreases by the opening of the permeability transition pore (PTP). These PTP are formed by the binding of Bax with adenine nucleotide translocator (ANT) and cause depolarization in the membrane. The depolarization releases apoptogenic factors (cytochrome c) that result in the loss of oxidative phosphorylation. Knockdown in lactate dehydrogenase (LDH) is the cause of the decrease in mitochondrial membrane potential elevating the levels of reactive oxygen species (ROS) and Bax. Consequently, causing an increase in the release of cytochrome c that ultimately leads to apoptosis. In this review, we have summarized the combined effect of mitochondrial membrane potential and LDH enzyme that triggers apoptosis in cells and their role in the mechanism of apoptosis.
细胞凋亡是一种程序性细胞死亡，是由于几种分解代谢酶的产生而发生的。在此过程中，线粒体发生了几种形态和生化变化，线粒体是参与细胞凋亡并控制凋亡途径的主要细胞器。在细胞凋亡过程中，细胞色素 c 从线粒体中释放出来，不同的蛋白质激活半胱天冬酶级联反应，使细胞向死亡过程发展。细胞凋亡主要是由于 p53 蛋白引起的，该蛋白允许异常细胞增殖。Bcl-2 和 Bcl-xl 是蛋白家族中的两种抗凋亡成员，可防止细胞凋亡。线粒体膜电位的下降是由通透性转换孔（PTP）的打开引起的。这些 PTP 是由 Bax 与腺嘌呤核苷酸转位酶（ANT）结合形成的，导致膜去极化。去极化释放细胞色素 c 等促凋亡因子，导致氧化磷酸化的丧失。乳酸脱氢酶（LDH）的敲低导致线粒体膜电位降低，从而增加活性氧（ROS）和 Bax 的水平。因此，导致细胞色素 c 的释放增加，最终导致细胞凋亡。在这篇综述中，我们总结了线粒体膜电位和 LDH 酶联合作用触发细胞凋亡及其在凋亡机制中的作用。
