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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)
Verlagsversion Forschungsdaten DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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24
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Sprache
Veröffentlichungsjahr 2017
HGF-Berichtsjahr 2017
ISSN (print) / ISBN 1350-9047
e-ISSN 1476-5403
Zeitschrift Cell Death and Differentiation
Quellenangaben Band: 24, Heft: 5, Seiten: 761-773 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Begutachtungsstatus Peer reviewed
Institut(e) 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
Forschungsfeld(er) Genetics and Epidemiology
Enabling and Novel Technologies
PSP-Element(e) 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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