Downregulation of Pink1 Influences Mitochondrial Fusion-fission Machinery and Sensitizes to Neurotoxins in Dopaminergic Cells

Overview

Journal Neurotoxicology

Specialties Environmental Health
Neurology
Toxicology

Date 2014 May 6

PMID 24792327

Citations 16

Authors

Liliana Rojas-Charry

Mark R Cookson

Andrea Nino

Humberto Arboleda

Gonzalo Arboleda

Affiliations

Soon will be listed here.

Abstract

It is now well established that mitochondria are organelles that, far from being static, are subject to a constant process of change. This process, which has been called mitochondrial dynamics, includes processes of both fusion and fission. Loss of Pink1 (PTEN-induced putative kinase 1) function is associated with early onset recessive Parkinson's disease and it has been proposed that mitochondrial dynamics might be affected by loss of the mitochondrial kinase. Here, we report the effects of silencing Pink1 on mitochondrial fusion and fission events in dopaminergic neuron cell lines. Cells lacking Pink1 were more sensitive to cell death induced by C2-Ceramide, which inhibits proliferation and induces apoptosis. In the same cell lines, mitochondrial morphology was fragmented and this was enhanced by application of forskolin, which stimulates the cAMP pathway that phosphorylates Drp1 and thereby inactivates it. Cells lacking Pink1 had lower Drp1 and Mfn2 expression. Based on these data, we propose that Pink1 may exert a neuroprotective role in part by limiting mitochondrial fission.

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