Honrath 2017 Cell Death Differ

From Bioblast
Publications in the MiPMap
Honrath B, Matschke L, Meyer T, Magerhans L, Perocchi F, Ganjam GK, Zischka H, Krasel C, Gerding A, Bakker BM, BΓΌnemann M, Strack S, Decher N, Culmsee C, Dolga AM (2017) SK2 channels regulate mitochondrial respiration and mitochondrial Ca2+ uptake. Cell Death Differ 24:761-73.

Β» PMID: 28282037

Honrath B, Matschke L, Meyer T, Magerhans L, Perocchi F, Ganjam GK, Zischka H, Krasel C, Gerding A, Bakker BM, BΓΌnemann M, Strack S, Decher N, Culmsee C, Dolga AM (2017) Cell Death Differ

Abstract: Mitochondrial calcium ([Ca2+]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 [Ca2+]m uptake upon SK channel activation as detected by time lapse mitochondrial Ca2+ measurements with the Ca2+-binding mitochondria-targeted aequorin and FRET-based [Ca2+]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 [Ca2+]m uptake and mitochondrial respiration in conditions, where sustained mitochondrial damage determines progressive neuronal death. β€’ Keywords: HT22 mouse hippocampal neuronal cell s β€’ Bioblast editor: Kandolf G β€’ O2k-Network Lab: NL Groningen Reijngoud RJ, DE Munich Zischka H, DE Munich Perocchi F


Labels: MiParea: Respiration, Genetic knockout;overexpression, Pharmacology;toxicology  Pathology: Neurodegenerative 

Organism: Mouse  Tissue;cell: Nervous system, Other cell lines  Preparation: Isolated mitochondria 


Coupling state: LEAK, OXPHOS, ET  Pathway:HRR: Oxygraph-2k 

2017-05 

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