Methylmalonic acidemia triggers lysosomal-autophagy dysfunctions.

ABSTRACT:

Background

Methylmalonic acidemia (MMA) is a rare inborn error of propionate metabolism caused by deficiency of the mitochondrial methylmalonyl-CoA mutase (MUT) enzyme. As matter of fact, MMA patients manifest impairment of the primary metabolic network with profound damages that involve several cell components, many of which have not been discovered yet. We employed cellular models and patients-derived fibroblasts to refine and uncover new pathologic mechanisms connected with MUT deficiency through the combination of multi-proteomics and bioinformatics approaches.

Results

Our data show that MUT deficiency is connected with profound proteome dysregulations, revealing molecular actors involved in lysosome and autophagy functioning. To elucidate the effects of defective MUT on

SUBMITTER: Costanzo M 

PROVIDER: S-EPMC11102240 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature