title: Downregulation of Pink1 influences mitochondrial fusion-fission machinery and sensitizes to neurotoxins in dopaminergic cells.
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.
authors.affiliation: Grupos de Neurociencias y Muerte Celular, Facultad de Medicina e Instituto de Genética, Universidad Nacional de Colombia, Bogotá, Colombia.
authors.forename: Liliana
authors.initials: L
authors.lastname: Rojas-Charry
authors.affiliation: Laboratory of Neurogenetics, National Institute of Aging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Cookson
authors.affiliation: Grupos de Neurociencias y Muerte Celular, Facultad de Medicina e Instituto de Genética, Universidad Nacional de Colombia, Bogotá, Colombia.
authors.forename: Andrea
authors.initials: A
authors.lastname: Niño
authors.affiliation: Grupos de Neurociencias y Muerte Celular, Facultad de Medicina e Instituto de Genética, Universidad Nacional de Colombia, Bogotá, Colombia.
authors.forename: Humberto
authors.initials: H
authors.lastname: Arboleda
authors.affiliation: Grupos de Neurociencias y Muerte Celular, Facultad de Medicina e Instituto de Genética, Universidad Nacional de Colombia, Bogotá, Colombia. Electronic address: gharboledab@unal.edu.co.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Arboleda
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012402:Rotenone / Q000633:toxicity; D013110:Sphingosine / Q000031:analogs & derivatives / Q000633:toxicity; D000099202:PTEN-Induced Putative Kinase
chemical_list: D024101:Mitochondrial Proteins; D011494:Protein Kinases; D012402:Rotenone; D013110:Sphingosine; D000099202:PTEN-Induced Putative Kinase; C064769:N-acetylsphingosine
keywords: Ceramide; Mitochondrial dynamics; Parkinson; Pink1; Rotenone