title: Hexokinase activity is required for recruitment of parkin to depolarized mitochondria.
abstract: Autosomal recessive parkinsonism genes contribute to maintenance of mitochondrial function. Two of these, PINK1 and parkin, act in a pathway promoting autophagic removal of depolarized mitochondria. Although recruitment of parkin to mitochondria is PINK1-dependent, additional components necessary for signaling are unclear. We performed a screen for endogenous modifiers of parkin recruitment to depolarized mitochondria and identified hexokinase 2 (HK2) as a novel modifier of depolarization-induced parkin recruitment. Hexose kinase activity was required for parkin relocalization, suggesting the effects are shared among hexokinases including the brain-expressed hexokinase 1 (HK1). Knockdown of both HK1 and HK2 led to a stronger block in parkin relocalization than either isoform alone, and expression of HK2 in primary neurons promoted YFP-parkin recruitment to depolarized mitochondria. Mitochondrial parkin recruitment was attenuated with AKT inhibition, which is known to modulate HK2 activity and mitochondrial localization. We, therefore, propose that Akt-dependent recruitment of hexokinases is a required step in the recruitment of parkin prior to mitophagy.
authors: Cell Biology and Gene Expression Section and.
authors: Melissa K
authors: MK
authors: McCoy
authors: Alice
authors: A
authors: Kaganovich
authors: Iakov N
authors: IN
authors: Rudenko
authors: Jinhui
authors: J
authors: Ding
authors: Mark R
authors: MR
authors: Cookson
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000502:physiology*; D063306:Mitophagy; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D006593:Hexokinase; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein; C472074:HK1 protein, human
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