Parkinson's disease-associated pathogenic VPS35 mutation causes complex I deficits

In this study, we aimed to determine whether pathogenic VPS35 mutation impacts the activity of complex I and its underlying mechanism. Indeed, VPS35 D620N mutation led to decreased enzymatic activity and respiratory defects in complex I and II in patient fibroblasts. While no changes in the expression of the complex I and II subunits were noted, the level of assembled complex I and II as well as the supercomplex was significantly reduced in D620N fibroblasts. Importantly, inhibition of mitochondrial fission rescued the contents of assembled complexes as well as the functional defects in complex I and II. Overall, these results suggest that VPS35 D620N mutation-induced excessive mitochondrial fission leads to the defects in the assembled complex I and supercomplex and causes bioenergetics deficits.
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research