[SCAN ITQB Alumni] Mitochondria Function and Parkinson’s Disease: the role of PINK1

SCAN ITQB Alumni

Title: Mitochondria Function and Parkinson’s Disease: the role of PINK1

Speaker: Vanessa Morais

Affiliation: Vanessa Morais Lab, IMM

¹ Instituto de Medicina Molecular iMM, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal

² VIB and KUL, Center for the Biology of Disease, Leuven, Belgium

Abstract:

The mitochondrial kinase PINK1, a gene that causes Parkinson’s Disease (PD), has further strengthened the involvement of mitochondrial dysfunction in PD. The fact that PINK1 regulates Complex I enzymatic activity resulting in loss of mitochondrial membrane potential and compromised synaptic activity suggests a role for this gene in mitochondrial maintenance. However, the underlying molecular mechanisms remain to be elucidated. Here we show that mitochondrial membrane potential is reduced in human PINK1 deficient fibroblasts. A complete phosphoproteome performed on Complex I identified the specific involvement of PINK1 in the phosphorylation of a Complex I subunit. Complex I enzymatic activity and mitochondrial membrane potential were restored when a constitutively pseudophosphorylated form of this subunit was used, as well as reported phenotypes in Drosophila pink1 mutants and deficits in patient fibroblasts were also restored. We conclude that an evolutionary conserved molecular pathway regulates Complex I activity via PINK1 kinase in Drosophila, mouse and human.