A new in vitro model to study mitochondria in Parkinson’s Disease

Parkinson’s disease (PD) is a pathogenically complex multifactorial disease and the most common neurodegenerative movement disorder. Several lines of evidence, obtained from studies of familial forms of PD, patient samples, and in vitro/in vivo models, underline a major role of mitochondrial dysfunction, impaired mitochondrial quality control, and dysregulated mitochondrial crosstalk with other organelles.
This project aimed to understand whether moderate overexpression of the inner mitochondrial membrane OPA1 would rescue the mitochondrial dysfunction caused by A53T mutant alpha-synuclein. The underlying rationale for this work was based on the fact that mild overexpression of OPA1 was recently demonstrated to improve the motor performance in addition to biochemical and molecular phenotypes of two mouse models of mitochondrial disease [328]; of note, in mice, mild OPA1 overexpression is compatible with normal development, fertility and lifespan [83]. Therefore, our intention was to cross the Opa1tg mouse with the A53T alpha-synuclein transgenic line M83 model [325] to analyse the mitochondrial phenotype in the double transgenic mouse.