SLC25A20

Last update 23 Jan 2025

Basic Info

Synonyms

CAC, CACT, carnitine-acylcarnitine carrier

+ [5]

Introduction

Mediates the electroneutral exchange of acylcarnitines (O-acyl-(R)-carnitine or L-acylcarnitine) of different acyl chain lengths (ranging from O-acetyl-(R)-carnitine to long-chain O-acyl-(R)-carnitines) with free carnitine ((R)-carnitine or L-carnitine) across the mitochondrial inner membrane, via a ping-pong mechanism (PubMed:12892634, PubMed:18307102) (Probable). Key player in the mitochondrial oxidation pathway, it translocates the fatty acids in the form of acylcarnitines into the mitochondrial matrix, where the carnitine palmitoyltransferase 2 (CPT-2) activates them to undergo fatty acid beta-oxidation (Probable). Catalyzes the unidirectional transport (uniport) of carnitine at lower rates than the antiport (exchange) (PubMed:18307102).

100 Clinical Results associated with SLC25A20

100 Translational Medicine associated with SLC25A20

0 Patents (Medical) associated with SLC25A20

266

Literatures (Medical) associated with SLC25A20

01 Mar 2025·Gene

Loss-of-function SLC25A20 variant causes carnitine-acylcarnitine translocase deficiency by reducing SLC25A20 protein stability

Article

Author: Zheng, Yingchun ; Wei, Xiaofeng ; Fan, Shushu ; Gan, Zhongzhi ; Zheng, Qiqi ; Xiong, Fu

BACKGROUND/AIMAutosomal-recessive carnitine-acylcarnitine translocase deficiency (CACTD) is a rare disorder of long-chain fatty acid oxidation caused by variants in the SLC25A20 gene, leading to energy deficiency and the toxic accumulation of long-chain acylcarnitines. Under fasting conditions, most newborns with severe CACTD experience sudden cardiac arrest and hypotonia, often leading to premature death due to rapid disease progression. The genetic factors and pathogenic mechanisms in CACTD are essential for its diagnosis, treatment, and prevention.METHODSWhole-exome sequencing was carried out on the CACTD patients. Bioinformatics analysis predicted the pathogenicity and three-dimensional structure of SLC25A20. Quantitative PCR was employed to detect changes in SLC25A20, CPT1A and CPT2 mRNA levels. The expression and stability of the variant protein were assessed via Western blot. Additionally, the subcellular localization of the variant protein was observed using immunofluorescence.RESULTSWe identified compound heterozygous pathogenic variants of SLC25A20 (c.476 T > C and c.199-10 T > G) in CACTD families, with patients exhibiting an abnormal carnitine spectrum. In vitro functional studies demonstrated that the c.476 T > C and c.199-10 T > G variants decreased the protein stability of SLC25A20, reduced CPT1A and CPT2 mRNA expression, and caused protein aggregation of SLC25A20.CONCLUSIONSWe propose that the decreased stability of the SLC25A20 variants c.476 T > C and c.199-10 T > G has the potential to lead to the development of CACTD by affecting the mitochondrial shuttle of acylcarnitine and carnitine, thereby inhibiting the β-oxidation pathway. Therefore, we believe these compound heterozygous variants (c.199-10 T > G and c.476 T > C) are loss-of-function variants. Our findings provide valuable data on CACTD pathogenesis and genotype-phenotype correlations.

26 Dec 2024·Current Alzheimer Research

Development of a Novel Mitochondrial Dysfunction-Related Alzheimer's Disease Diagnostic Model Using Bioinformatics and Machine Learning

Article

Author: Shi, Bin ; Zhang, Kuo ; Yang, Kai ; Yu, Gongchang

Introduction:Alzheimer's disease (AD) represents the most common neurodegenerative disorder, characterized by progressive cognitive decline and memory loss. Despite the recognition of mitochondrial dysfunction as a critical factor in the pathogenesis of AD, the specific molecular mechanisms remain largely undefined.Method:This study aimed to identify novel biomarkers and therapeutic strategies associated with mitochondrial dysfunction in AD by employing bioinformatics combined with machine learning methodologies. We performed Weighted Gene Co-expression Network Analysis (WGCNA) utilizing gene expression data from the NCBI Gene Expression Omnibus (GEO) database and isolated mitochondria-related genes through the MitoCarta3.0 database. By intersecting WGCNA-derived module genes with identified mitochondrial genes, we compiled a list of 60 mitochondrial dysfunction- related genes (MRGs) significantly enriched in pathways pertinent to mitochondrial function, such as the citrate cycle and oxidative phosphorylation.Results:Employing machine learning techniques, including random forest and LASSO, along with the CytoHubba algorithm, we identified key genes with strong diagnostic potential, such as ACO2, CS, MRPS27, SDHA, SLC25A20, and SYNJ2BP, verified through ROC analysis. Furthermore, an interaction network involving miRNA-MRGs-transcription factors and a protein-drug interaction network revealed potential therapeutic compounds such as Congo red and kynurenic acid that target MRGs.Conclusion:These findings delineate the intricate role of mitochondrial dysfunction in AD and highlight promising avenues for further exploration of biomarkers and therapeutic interventions in this devastating disease.

01 Dec 2024·Molecular Genetics and Metabolism Reports

Homozygous slc25a20 zebrafish mutant reveals insights into carnitine-acylcarnitine translocase deficiency pathogenesis

Article

Author: Yamanaka, Tomoyuki ; Toyokuni, Shinya ; Hishida, Ryuichi ; Ishiguro, Kohei ; Matsui, Hideaki

The SLC25A20 gene encodes carnitine-acylcarnitine translocase (CACT), facilitating the transport of long-chain acylcarnitine required for energy production via β-oxidation into the mitochondria. Loss-of-function mutations in this gene lead to CACT deficiency, a rare autosomal recessive disorder of fatty acid metabolism characterized by severe symptoms including cardiomyopathy, hepatic dysfunction, rhabdomyolysis, hypoketotic hypoglycemia, and hyperammonemia, often resulting in neonatal mortality. Here, we utilized CRISPR/Cas9 gene editing to isolate slc25a20 mutant zebrafish. Homozygous mutants displayed significant lethality, with the majority succumbing before reaching maturity. However, we identified a notably rare homozygous individual that survived into adulthood, prompting a histological examination. Firstly, we observed adipose tissue accumulation at various sites in the homozygous mutant. The mutant heart exhibited hypertrophy, along with degenerated myocardial and muscle cells containing numerous eosinophilic nuclei. Additionally, we found no large oil droplet vacuoles in the mutant liver; however, the hepatocytes displayed numerous small vacuoles resembling lipid droplets. Iron deposition was evident in the spleen and parts of the liver. Overall, our slc25a20 zebrafish mutant displayed tissue pathologies analogous to human CACT deficiency, suggesting its potential as a pathological model contributing to the elucidation of pathogenesis and the improvement/development of therapies for CACT deficiency.

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