L-DOPA causes mitochondrial dysfunction in vitro: a novel mechanism of L-DOPA toxicity uncovered.

L-DOPA causes mitochondrial dysfunction in vitro: a novel mechanism of L-DOPA toxicity uncovered. Int J Biochem Cell Biol. 2019 Oct 22;:105624 Authors: Giannopoulos S, Samardzic K, Raymond BBA, Djordjevic SP, Rodgers KJ Abstract In Parkinson's disease (PD), as in many other neurodegenerative disorders, mitochondrial dysfunction, protein misfolding, and proteotoxic stress underly the disease process. For decades, the primary symptomatic treatment for PD has been the dopamine precursor L-DOPA (Levodopa). L-DOPA however can initiate protein misfolding through its ability to mimic the protein amino acid L-tyrosine, resulting in random errors in aminoacylation and L-DOPA becoming mistakenly inserted into the polypeptide chain of proteins in place of L-tyrosine. In the present study we examined the impact that the generation of DOPA-containing proteins had on human neuroblastoma cell (SH-SY5Y) function in vitro. We showed that even in the presence of antioxidants there was a significant accumulation of cytosolic ubiquitin in DOPA-treated cells, an upregulation in the endosomal-lysosomal degradation system, deleterious changes to mitochondrial morphology and a marked decline in mitochondrial function.The effects of L-DOPA on mitochondrial function were not observed with D-DOPA, the stereoisomer of L-DOPA that cannot be inserted into proteins so did not result from oxidative stress. We could fully protect against these effects by co-treatmen...
Source: The International Journal of Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Int J Biochem Cell Biol Source Type: research