Acyl-CoA Synthetase Long-Chain Isoenzymes in Kidney Diseases: Mechanistic Insights and Therapeutic Implications

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Cell Biochemistry and Function Pub Date : 2024-08-30 DOI:10.1002/cbf.4114

Swati Mishra, Vishwadeep Shelke, Anil Bhanudas Gaikwad

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Abstract

Long-chain acyl-CoA synthetases (ACSLs) are pivotal enzymes in fatty acid metabolism, essential for maintaining cellular homeostasis and energy production. Recent research has uncovered their significant involvement in the pathophysiology of various kidney diseases, including acute kidney injury (AKI), chronic kidney disease (CKD), diabetic kidney disease (DKD), and renal cell carcinoma (RCC). While ACSL1, ACSL3, ACSL4, and ACSL5 have been extensively studied for their roles in processes such as ferroptosis, lipid peroxidation, renal fibrosis, epithelial-mesenchymal transition, and tumor progression, the role of ACSL6 in kidney diseases remain largely unexplored. Notably, these isoenzymes exhibit distinct functions in different kidney diseases. Therefore, to provide a comprehensive understanding of their involvement, this review highlights the molecular pathways influenced by ACSLs and their roles in modulating cell death, inflammation, and fibrosis during kidney disease progression. By examining these mechanisms in detail, this review underscores the potential of ACSLs as biomarkers and therapeutic targets, advocating for further research to elucidate the precise roles of individual ACSL isoenzymes in kidney disease progression. Understanding these mechanisms opens new avenues for developing targeted interventions and improving therapeutic outcomes for patients with kidney diseases.

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肾脏疾病中的酰基-CoA 合成酶长链异酶：机理认识和治疗意义

长链酰基-CoA 合成酶（ACSL）是脂肪酸代谢中的关键酶，对维持细胞平衡和能量生产至关重要。最近的研究发现，它们在急性肾损伤（AKI）、慢性肾病（CKD）、糖尿病肾病（DKD）和肾细胞癌（RCC）等多种肾脏疾病的病理生理学中发挥着重要作用。ACSL1、ACSL3、ACSL4 和 ACSL5 在铁变态反应、脂质过氧化、肾脏纤维化、上皮-间质转化和肿瘤进展等过程中的作用已被广泛研究，但 ACSL6 在肾脏疾病中的作用在很大程度上仍未被探索。值得注意的是，这些同工酶在不同的肾脏疾病中表现出不同的功能。因此，为了全面了解它们的参与情况，本综述重点介绍了受 ACSLs 影响的分子通路及其在肾脏疾病进展过程中调节细胞死亡、炎症和纤维化的作用。通过详细研究这些机制，本综述强调了 ACSLs 作为生物标志物和治疗靶点的潜力，提倡进一步研究以阐明单个 ACSL 同工酶在肾病进展中的确切作用。了解这些机制为开发有针对性的干预措施和改善肾病患者的治疗效果开辟了新途径。

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来源期刊

Cell Biochemistry and Function 生物-生化与分子生物学

CiteScore

6.20

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Cell Biochemistry and Function publishes original research articles and reviews on the mechanisms whereby molecular and biochemical processes control cellular activity with a particular emphasis on the integration of molecular and cell biology, biochemistry and physiology in the regulation of tissue function in health and disease. The primary remit of the journal is on mammalian biology both in vivo and in vitro but studies of cells in situ are especially encouraged. Observational and pathological studies will be considered providing they include a rational discussion of the possible molecular and biochemical mechanisms behind them and the immediate impact of these observations to our understanding of mammalian biology.