Centre for Life Sciences, Chitkara School of Health Sciences, Chitkara University, Rajpura, Punjab, 140401, India.
Mol Biol Rep. 2023 Apr;50(4):3849-3862. doi: 10.1007/s11033-023-08299-3. Epub 2023 Jan 30.
FF adenosine triphosphate (ATP) synthase, also known as the complex V, is the central ATP-producing unit in the cells arranged in the mitochondrial and plasma membranes. FF ATP synthase also regulates the central metabolic processes in the human body driven by proton motive force (Δp). Numerous studies have immensely contributed toward highlighting its regulation in improving energy homeostasis and maintaining mitochondrial integrity, which otherwise gets compromised in illnesses. Yet, its role in the implication of non-communicable diseases remains unknown. FF ATP synthase dysregulation at gene level leads to reduced activity and delocalization in the cristae and plasma membranes, which is directly associated with non-communicable diseases: cardiovascular diseases, diabetes, neurodegenerative disorders, cancer, and renal diseases. Individual subunits of the FF ATP synthase target ligand-based competitive or non-competitive inhibition. After performing a systematic literature review to understand its specific functions and its novel drug targets, the present article focuses on the central role of FF ATP synthase in primary non-communicable diseases. Next, it discusses its involvement through various pathways and the effects of multiple inhibitors, activators, and modulators specific to non-communicable diseases with a futuristic outlook.
FF 三磷酸腺苷（ATP）合酶，也称为复合物 V，是在线粒体膜和质膜中排列的细胞中产生 ATP 的核心单元。FF ATP 合酶还通过质子动力势（Δp）调节人体的中心代谢过程。大量研究极大地促进了其在改善能量稳态和维持线粒体完整性方面的调节作用，否则这些作用在疾病中会受到损害。然而，其在非传染性疾病中的作用仍然未知。FF ATP 合酶在基因水平上的失调会导致活性降低和在嵴和质膜中的定位改变，这与非传染性疾病直接相关：心血管疾病、糖尿病、神经退行性疾病、癌症和肾脏疾病。FF ATP 合酶的各个亚基都是以配体为基础的竞争性或非竞争性抑制剂的靶标。在进行系统的文献综述以了解其特定功能和新的药物靶点后，本文重点关注 FF ATP 合酶在原发性非传染性疾病中的核心作用。接下来，它通过多种途径讨论了其参与情况，以及针对非传染性疾病的多种抑制剂、激活剂和调节剂的作用，并对未来进行了展望。
