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Honrath, B.* ; Matschke, L.* ; Meyer, T.* ; Magerhans, L.* ; Perocchi, F. ; Ganjam, G.K.* ; Zischka, H. ; Krasel, C.* ; Gerding, A.* ; Bakker, B.M.* ; Bünemann, M.* ; Strack, S.* ; Decher, N.* ; Culmsee, C.* ; Dolga, A.M.*

SK2 channels regulate mitochondrial respiration and mitochondrial Ca2+ uptake.

Cell Death Differ. 24, 761-773 (2017)
Publ. Version/Full Text Research data DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Mitochondrial calcium ([Ca(2+)]m) overload and changes in mitochondrial metabolism are key players in neuronal death. Small conductance calcium-activated potassium (SK) channels provide protection in different paradigms of neuronal cell death. Recently, SK channels were identified at the inner mitochondrial membrane, however, their particular role in the observed neuroprotection remains unclear. Here, we show a potential neuroprotective mechanism that involves attenuation of [Ca(2+)]m uptake upon SK channel activation as detected by time lapse mitochondrial Ca(2+) measurements with the Ca(2+)-binding mitochondria-targeted aequorin and FRET-based [Ca(2+)]m probes. High-resolution respirometry revealed a reduction in mitochondrial respiration and complex I activity upon pharmacological activation and overexpression of mitochondrial SK2 channels resulting in reduced mitochondrial ROS formation. Overexpression of mitochondria-targeted SK2 channels enhanced mitochondrial resilience against neuronal death, and this effect was inhibited by overexpression of a mitochondria-targeted dominant-negative SK2 channel. These findings suggest that SK channels provide neuroprotection by reducing [Ca(2+)]m uptake and mitochondrial respiration in conditions, where sustained mitochondrial damage determines progressive neuronal death.
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Publication type Article: Journal article
Document type Scientific Article
Language
Publication Year 2017
HGF-reported in Year 2017
ISSN (print) / ISBN 1350-9047
e-ISSN 1476-5403
Journal Cell Death and Differentiation
Quellenangaben Volume: 24, Issue: 5, Pages: 761-773 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)
Institute of Molecular Toxicology and Pharmacology (TOX)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30203 - Molecular Targets and Therapies
Research field(s) Genetics and Epidemiology
Enabling and Novel Technologies
PSP Element(s) G-553000-001
G-505200-003
DOI 10.1038/cdd.2017.2
WOS ID WOS:000400655600002
Scopus ID 85014771597
PubMed ID 28282037
Erfassungsdatum 2017-06-08
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