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Difference between revisions of "Heeman 2011 J Cell Sci"

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|instruments=Oxygraph-2k
|instruments=Oxygraph-2k
|injuries=RONS; Oxidative Stress, Mitochondrial Disease; Degenerative Disease and Defect
|injuries=RONS; Oxidative Stress, Mitochondrial Disease; Degenerative Disease and Defect
|diseases=Parkinson's disease
|organism=Mouse
|organism=Mouse
|preparations=Intact Cell; Cultured; Primary
|preparations=Intact Cell; Cultured; Primary
}}
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Revision as of 15:00, 14 March 2013

Publications in the MiPMap
Heeman B, Van den Haute C, Aelvoet SA, Valsecchi F, Rodenburg RJ, Reumers V, Debyser Z, Callewaert G, Koopman WJ, Willems PH, Baekelandt V (2011) Depletion of PINK1 affects mitochondrial metabolism, calcium homeostasis and energy maintenance. J Cell Sci 124: 1115-1125.

Β» PMID:21385841

Heeman B, Van den Haute C, Aelvoet SA, Valsecchi F, Rodenburg RJ, Reumers V, Debyser Z, Callewaert G, Koopman WJ, Willems PH, Baekelandt V (2011) J Cell Sci

Abstract: Loss-of-function mutations in the gene encoding the mitochondrial PTEN-induced putative kinase 1 (PINK1) are a major cause of early-onset familial Parkinson's disease (PD). Recent studies have highlighted an important function for PINK1 in clearing depolarized mitochondria by mitophagy. However, the role of PINK1 in mitochondrial and cellular functioning in physiological conditions is still incompletely understood. Here, we investigate mitochondrial and cellular calcium (Ca(2+)) homeostasis in PINK1-knockdown and PINK1-knockout mouse cells, both in basal metabolic conditions and after physiological stimulation, using unbiased automated live single-cell imaging in combination with organelle-specific fluorescent probes. Our data reveal that depletion of PINK1 induces moderate fragmentation of the mitochondrial network, mitochondrial membrane depolarization and increased production of reactive oxygen species. This results in reduced uptake of Ca(2+) by mitochondria after physiological stimulation. As a consequence, cells with knockdown or knockout of PINK1 display impaired mitochondrial ATP synthesis, which is exacerbated under conditions of increased ATP demand, thereby affecting cytosolic Ca(2+) extrusion. The impairment in energy maintenance was confirmed in the brain of PINK1-knockout mice by in vivo bioluminescence imaging. Our findings demonstrate a key role for PINK1 in the regulation of mitochondrial homeostasis and energy metabolism under physiological conditions. β€’ Keywords: PTEN- induced putative kinase 1 (PINK1)

β€’ O2k-Network Lab: NL Nijmegen Koopman WJ


Labels: Pathology: Parkinson's disease"Parkinson's disease" is not in the list (Aging;senescence, Alzheimer's, Autism, Cancer, Cardiovascular, COPD, Diabetes, Inherited, Infectious, Myopathy, ...) of allowed values for the "Diseases" property.  Stress:RONS; Oxidative Stress"RONS; Oxidative Stress" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property., Mitochondrial Disease; Degenerative Disease and Defect"Mitochondrial Disease; Degenerative Disease and Defect" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property.  Organism: Mouse 

Preparation: Intact Cell; Cultured; Primary"Intact Cell; Cultured; Primary" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property. 



HRR: Oxygraph-2k