Lysosomal dysfunction impairs mitochondrial quality control and is associated with neurodegeneration in TBCK encephaloneuronopathy.

ABSTRACT: Biallelic variants in the TBCK gene cause intellectual disability with remarkable clinical variability, ranging from static encephalopathy to progressive neurodegeneration (TBCK-Encephaloneuronopathy). The biological factors underlying variable disease penetrance remain unknown. Since previous studies had suggested aberrant autophagy, we tested whether mitophagy and mitochondrial function are altered in TBCK ^-/- fibroblasts derived from patients exhibiting variable clinical severity. Our data show significant accumulation of mitophagosomes, reduced mitochondrial respiratory capacity and mitochondrial DNA content, suggesting impaired mitochondrial quality control. Furthermore, the degree of mitochondrial dysfunction correlates with a neurodegenerative clinical cours

SUBMITTER: Tintos-Hernandez JA 

PROVIDER: S-EPMC8603245 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature