Bioinformatics-based study on the pathogenic mechanism of vitiligo caused by mitochondrial dysfunction

Objective To investigate the mechanisms of mitochondrial dysfunction-induced vitiligo based on bioinformatics. Methods The vitiligo target genes were obtained from CTD/Gene Cards/OMIM/NCBI Gene databases, while mitochondrial dysfunction target genes were downloaded from the MITOMAP database, followed by intersection analysis to identify the common genes. The latter were subjected to GO and KEGG enrichment analysis. The core genes were screened by analysis of protein-protein interaction. The NetworkAnalyst and Toppgene databases were used to predict the core gene-related transcription factors, miRNAs and the treatments. Results There were 90 common genes in vitiligo and mitochondrial dysfunction, and 13 core genes were screened by analysis of protein-protein interaction. The biological processes of the common genes were mainly enriched in mitochondrial respiratory chain complex assembly, while the cellular components were mainly enriched in mitochondria. The molecular functions were mainly enriched in the activities of redox-driven transmembrane transporter and oxidoreductase, and KEGG was mainly enriched in respiratory electron transport. The transcription factors with high degree of interactions with the core genes included ATF1, KDM5A, KDM5B and PHF8, and the miRNAs with high interaction with core genes included hsa-mir-1-3p and hsa-mir-16-5p. The predicted effective drugs were lipoic acid and ubiquinols. Conclusions Mitochondrial dysfunction may contribute to pathogenesis of vitiligo by affecting biological processes, such as complex assembly and electron transport in the mitochondrial respiratory chain. Transcription factors, such as ATF1 and KDM5, and miRNAs, including miR-1 and miR-493, may play an important pathogenic role in vitiligo by interaction with key genes, such as NDUFA9, SURF1, NDUFS1, NDUFS4 and LRPPRC.