Phosphorylation of the mitochondrial ATP-sensitive potassium channel occurs independently of PKCε in turtle brain

Hawrysh, Peter John; Miles, Ashley Rebecca; Buck, Leslie T.

doi:10.1016/j.cbpb.2016.06.002

Cited by 3 publications

(1 citation statement)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With regard to the reduction of Drp1-dependent mitochondrial fission when kir6.2 is absent, two conjectures are presented. First, as mitochondrial membranes express the functional KATP channel (Raval et al, 2007;Hawrysh et al, 2016;Paggio et al, 2019), the ectopic expression of kir6.2 in astrocytes may be a component of mitochondrial KATP which regulates organelle functions. Second, KATP in cell membranes regulates the cellular calcium signal that is crucial for mitochondrial quality control, including mitochondrial fission/fusion (Lovy et al, 2020;Zhang et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Induced Expression of kir6.2 in A1 Astrocytes Propagates Inflammatory Neurodegeneration via Drp1-dependent Mitochondrial Fission

Song

Zhu

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Glia-mediated inflammatory processes are crucial in the pathogenesis of Parkinson’s disease (PD). As the most abundant cells of the brain and active participants in neuroinflammatory responses, astrocytes largely propagate inflammatory signals and amplify neuronal loss. Hence, intensive control of astrocytic activation is necessary to prevent neurodegeneration. In this study, we report that the astrocytic kir6.2, as a abnormal response after inflammatory stimuli, promotes the reactivity of A1 neurotoxic astrocytes. Using kir6.2 knockout (KO) mice, we find reversal effects of kir6.2 deficiency on A1-like astrocyte activation and death of dopaminergic neurons in lipopolysaccharide (LPS)-induced mouse models for PD. Further in vitro experiments show that aberrant kir6.2 expression induced by inflammatory irritants in astrocytes mediates the dynamin-related protein 1 (Drp1)-dependent excessive mitochondrial fragmentation and results in mitochondrial malfunctions. By deleting kir6.2, astrocytic activation is reduced and astrocytes-derived neuronal injury is prevented. We therefore conclude that astrocytic kir6.2 can potentially elucidate the pathology of PD and promote the development of therapeutic strategies for PD.

show abstract