Mitochondrial microRNAs Are Dysregulated in Patients with Fabry Disease

Fabry disease (FD) is a lysosomal storage disorder caused by mutations in the gene for alpha-galactosidase A, inducing a progressive accumulation of globotriaosylceramide (GB3) and its metabolites in different organs and tissues. GB3 deposition does not fully explain the clinical manifestations of FD, and other pathogenetic mechanisms have been proposed, requiring the identification of new biomarkers for monitoring FD patients. Emerging evidence suggests the involvement of mitochondrial alterations in FD. Here, we propose mitochondrial-related microRNAs (miRs) as potential biomarkers of mitochondrial involvement in FD. Indeed, we demonstate that miRs regulating different aspects of mitochondrial homeostasis including expression and assembly of respiratory chain, mitogenesis, antioxidant capacity, and apoptosis are consistently dysregulated in FD patients. Our data unveil a novel noncoding RNA signature of FD patients, indicating mitochondrial-related miRs as new potential pathogenic players and biomarkers in FD.

Automated summary

Fabry disease is a lysosomal storage disorder caused by mutations in the gene for alpha-galactosidase A, leading to the accumulation of globotriaosylceramide. The clinical manifestations of the disease cannot be fully explained by the accumulation of globotriaosylceramide, and other mechanisms are proposed, necessitating the identification of new biomarkers for monitoring Fabry disease patients.