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Reduction of PINK1 or DJ-1 impair mitochondrial motility in neurites and alter ER-mitochondria contacts

2018; Wiley; Volume: 22; Issue: 11 Linguagem: Inglês

10.1111/jcmm.13815

1582-4934

Cristina Parrado‐Fernández, Bernadette Schreiner, Maria Ankarcrona, Melissa M. Conti, Mark Cookson, Miia Kivipelto, Ángel Cedazo‐Mínguez, Anna Matton,

Autophagy in Disease and Therapy

Abstract Subcellular distribution of mitochondria in neurons is crucial for meeting the energetic demands, as well as the necessity to buffer Ca 2+ within the axon, dendrites and synapses. Mitochondrial impairment is an important feature of Parkinson disease ( PD ), in which both familial parkinsonism genes DJ ‐1 and PINK 1 have a great impact on mitochondrial function. We used differentiated human dopaminergic neuroblastoma cell lines with stable PINK 1 or DJ ‐1 knockdown to study live motility of mitochondria in neurites. The frequency of anterograde and retrograde mitochondrial motility was decreased in PINK 1 knockdown cells and the frequency of total mitochondrial motility events was reduced in both cell lines. However, neither the distribution nor the size of mitochondria in the neurites differed from the control cells even after downregulation of the mitochondrial fission protein, Drp1. Furthermore, mitochondria from PINK 1 knockdown cells, in which motility was most impaired, had increased levels of GSK 3βSer9 and higher release of mitochondrial Ca 2+ when exposed to CCCP ‐induced mitochondrial uncoupling. Further analysis of the ER ‐mitochondria contacts involved in Ca 2+ shuttling showed that PINK 1 knockdown cells had reduced contacts between the two organelles. Our results give new insight on how PINK 1 and DJ ‐1 influence mitochondria, thus providing clues to novel PD therapies.