positive regulation of synaptic transmission, dopaminergic / positive regulation of free ubiquitin chain polymerization / tRNA import into mitochondrion / TOM complex / positive regulation of cristae formation / voltage-gated monoatomic anion channel activity / mitochondrial transmembrane transport / mitochondrial outer membrane permeabilization / regulation of protein targeting to mitochondrion / Mitochondrial calcium ion transport ...positive regulation of synaptic transmission, dopaminergic / positive regulation of free ubiquitin chain polymerization / tRNA import into mitochondrion / TOM complex / positive regulation of cristae formation / voltage-gated monoatomic anion channel activity / mitochondrial transmembrane transport / mitochondrial outer membrane permeabilization / regulation of protein targeting to mitochondrion / Mitochondrial calcium ion transport / mitochondrion to lysosome vesicle-mediated transport / maintenance of protein location in mitochondrion / mitochondrion targeting sequence binding / establishment of protein localization to mitochondrion / protein kinase B binding / mitochondrial outer membrane translocase complex / cellular response to hydrogen sulfide / Lewy body / phospholipid scramblase activity / regulation of autophagy of mitochondrion / protein insertion into mitochondrial outer membrane / ceramide binding / regulation of synaptic vesicle transport / TORC2 signaling / negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway / mitochondria-associated endoplasmic reticulum membrane contact site / migrasome / positive regulation of mitochondrial electron transport, NADH to ubiquinone / regulation of hydrogen peroxide metabolic process / regulation of oxidative phosphorylation / negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway / C3HC4-type RING finger domain binding / regulation of cellular response to oxidative stress / protein-transporting ATPase activity / dopamine secretion / voltage-gated monoatomic ion channel activity / negative regulation of autophagosome assembly / positive regulation of dopamine secretion / binding of sperm to zona pellucida / autophagy of mitochondrion / phosphatidylcholine binding / oxysterol binding / positive regulation of type 2 mitophagy / Mitochondrial protein import / cellular response to toxic substance / negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / regulation of mitochondrion organization / monoatomic anion transport / negative regulation of JNK cascade / positive regulation of ubiquitin-protein transferase activity / positive regulation of protein targeting to mitochondrion / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / regulation of reactive oxygen species metabolic process / peptidase activator activity / phospholipid translocation / protein targeting to mitochondrion / cholesterol binding / astrocyte projection / porin activity / positive regulation of mitochondrial fission / negative regulation of macroautophagy / negative regulation of mitophagy / pore complex / FOXO-mediated transcription of cell death genes / negative regulation of intrinsic apoptotic signaling pathway / protein import into mitochondrial matrix / positive regulation of release of cytochrome c from mitochondria / positive regulation of ATP biosynthetic process / negative regulation of reactive oxygen species metabolic process / hemopoiesis / mitochondrial nucleoid / positive regulation of macroautophagy / protein transmembrane transporter activity / regulation of protein ubiquitination / negative regulation of mitochondrial fission / regulation of protein-containing complex assembly / mitophagy / monoatomic ion transport / sperm midpiece / regulation of proteasomal protein catabolic process / acrosomal vesicle / positive regulation of translation / response to ischemia / positive regulation of protein ubiquitination / PINK1-PRKN Mediated Mitophagy / cell periphery / regulation of mitochondrial membrane potential / respiratory electron transport chain / mitochondrion organization / macroautophagy / mitochondrial membrane / regulation of protein stability / mitochondrial intermembrane space / kinase binding / kinase activity / unfolded protein binding / cell body / growth cone / cellular response to oxidative stress / response to oxidative stress 類似検索 - 分子機能
PINK1, protein kinase domain / Mitochondrial import receptor subunit TOM5, metazoa / Mitochondrial import receptor subunit TOM6 homologue / Mitochondrial import receptor subunit TOM6 homolog / Eukaryotic mitochondrial porin signature. / Porin, eukaryotic type / Protein import receptor MAS20, metazoan / Protein import receptor MAS20 / Mitochondrial outer membrane translocase complex, Tom20 domain superfamily / MAS20 protein import receptor ...PINK1, protein kinase domain / Mitochondrial import receptor subunit TOM5, metazoa / Mitochondrial import receptor subunit TOM6 homologue / Mitochondrial import receptor subunit TOM6 homolog / Eukaryotic mitochondrial porin signature. / Porin, eukaryotic type / Protein import receptor MAS20, metazoan / Protein import receptor MAS20 / Mitochondrial outer membrane translocase complex, Tom20 domain superfamily / MAS20 protein import receptor / : / Mitochondrial outer membrane translocase complex, subunit Tom5 / Mitochondrial import receptor subunit or translocase / Mitochondrial import receptor subunit Tom22 / Mitochondrial import receptor subunit TOM7 / Mitochondrial import receptor subunit Tom22 / TOM7 family / Tom40 / Eukaryotic porin/Tom40 / Eukaryotic porin / Porin domain superfamily / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily 類似検索 - ドメイン・相同性
National Health and Medical Research Council (NHMRC, Australia)
GNT1178122
オーストラリア
Other private
引用
ジャーナル: Science / 年: 2025 タイトル: Structure of human PINK1 at a mitochondrial TOM-VDAC array. 著者: Sylvie Callegari / Nicholas S Kirk / Zhong Yan Gan / Toby Dite / Simon A Cobbold / Andrew Leis / Laura F Dagley / Alisa Glukhova / David Komander / 要旨: Mutations in the ubiquitin kinase PINK1 cause early-onset Parkinson's disease, but how PINK1 is stabilized at depolarized mitochondrial translocase complexes has remained poorly understood. We ...Mutations in the ubiquitin kinase PINK1 cause early-onset Parkinson's disease, but how PINK1 is stabilized at depolarized mitochondrial translocase complexes has remained poorly understood. We determined a 3.1-angstrom resolution cryo-electron microscopy structure of dimeric human PINK1 stabilized at an endogenous array of mitochondrial translocase of the outer membrane (TOM) and voltage-dependent anion channel (VDAC) complexes. Symmetric arrangement of two TOM core complexes around a central VDAC2 dimer is facilitated by TOM5 and TOM20, both of which also bind PINK1 kinase C-lobes. PINK1 enters mitochondria through the proximal TOM40 barrel of the TOM core complex, guided by TOM7 and TOM22. Our structure explains how human PINK1 is stabilized at the TOM complex and regulated by oxidation, uncovers a previously unknown TOM-VDAC assembly, and reveals how a physiological substrate traverses TOM40 during translocation.