RRC ID 85259
Author Howden JH, Hakansson H, Nieto-Rostro M, McAdam R, Arber C, Brandon NJ, Kittler JT.
Title Hexokinase 2 interacts with PINK1 to facilitate mitophagy in astrocytes and restrain inflammation-induced neurotoxicity.
Journal Cell Rep
Abstract Mitochondria are essential for ATP production, calcium buffering, and apoptotic signaling, with mitophagy playing a critical role in removing dysfunctional mitochondria. This study demonstrates that PINK1-dependent mitophagy occurs more rapidly and is less spatially restricted in astrocytes compared to neurons. We identified hexokinase 2 (HK2) as a key regulator of mitophagy in astrocytes, forming a glucose-dependent complex with PINK1 in response to mitochondrial damage. Additionally, exposure to neuroinflammatory stimuli enhances PINK1/HK2-dependent mitophagy, providing neuroprotection. These findings contribute to our understanding of mitophagy mechanisms in astrocytes and underscore the importance of PINK1 in cellular health and function within the context of neurodegenerative diseases.
Volume 44(6)
Pages 115809
Published 2025-6-24
DOI 10.1016/j.celrep.2025.115809
PII S2211-1247(25)00580-7
PMID 40531619
MeSH Animals Astrocytes* / metabolism Astrocytes* / pathology Hexokinase* / metabolism Humans Inflammation* / metabolism Inflammation* / pathology Mice Mice, Inbred C57BL Mitochondria / metabolism Mitophagy* Neurons / metabolism Neurons / pathology Protein Kinases* / metabolism
IF 8.109
Resource
DNA material mito-SRAI_pcDNA3 (RDB18223)