ライフサイエンスコーパス: parkin

1 creased mitophagy and the associated protein Parkin.

2 son's disease-associated E3 ubiquitin ligase Parkin.

3 n and degradation of the E3 ubiquitin ligase parkin.

4 se a loss of function of the encoded protein Parkin.

5 g in poorer autoinhibition in phosphorylated parkin.

6 IF-1alpha as a major ubiquitination site for Parkin.

7 e mitochondrial outer membrane and activates Parkin.

8 o suppressed VDAC1-induced redistribution of Parkin.

9 re marked for disposal via ubiquitylation by Parkin.

10 g PTEN-induced putative kinase 1 (PINK1) and parkin.

11 iKO prevented HFD-induced downregulation of parkin.

12 tivation to be independent of both PINK1 and Parkin.

13 Correspondingly, targeted knockdown of Parkin, a canonical E3 ubiquitin ligase important for mi

14 Knockdown of parkin, a positive regulator of mitophagy, dramatically

15 , our work demonstrates the critical role of PARKIN abundance, identifies regulating genes, and revea

16 gned to discover physiological regulators of PARKIN abundance, we performed a pooled genome-wide CRIS

17 entified and negatively regulates endogenous PARKIN abundance.

18 ormation with menadione (MN), led to phospho-Parkin accumulation in fragmented mitochondria resulting

19 The data suggest that parkin activation by Mdm2 could be targeted to increase

20 This effect was dependent on Parkin activation by PINK1 and accompanied by an increas

21 sorafenib as a mitocan and suggest that high Parkin activity levels could make tumor cells more sensi

22 sphomimetic ubiquitin in cells with residual Parkin activity.

23 domains from elimination by unchecked PINK1-Parkin activity.

24 expressed Mdm2 might enhance cytoprotective parkin activity.

25 Our results suggest that Parkin affects mtDNA levels in a mitophagy-independent m

26 Surprisingly however, mice deleted for Parkin alone are rather asymptomatic for PD-related path

27 , MN-induced mitophagy led to degradation of Parkin along with sequestration of Drp1 and PINK1 that w

28 related proteins-alpha-synuclein, LRRK2, and Parkin-alpha-synuclein might be a major link.

29 Here we find that Parkin (also known as PARK2), an E3 ubiquitin ligase imp

30 Parkin, an E3 ubiquitin ligase involved in Parkinson's d

31 Mutations in the PARK2 gene encoding parkin, an E3 ubiquitin ligase, are associated with auto

32 ggest a functional epistatic relationship to Parkin and a protective role of SLP-2 in neurons.

33 s provide novel evidence of USP13 effects on parkin and alpha-synuclein metabolism and suggest that U

34 We found that USP13 independently regulates parkin and alpha-synuclein ubiquitination in models of a

35 es in USP13 levels can affect two molecules, parkin and alpha-synuclein, that are implicated in PD pa

36 These results indicate that while both Parkin and CUL9 participate in mitochondrial quality con

37 verall, our study supports diverse roles for Parkin and demonstrates that nuclear Parkin regulates tr

38 KI links mitochondrial stress with the PINK1/Parkin and DJ-1 mechanisms of mitophagy.

39 dependent protein kinase regulates the PINK1/Parkin and DJ-1 pathways of mitophagy during sepsis.

40 ther E3 ubiquitin ligase Mdm2 directly binds parkin and enhances its enzymatic activity in vitro and

41 e generated mice deficient for both Cul9 and Parkin and examined them for PD-related phenotypes.

42 ributes to the tumor-suppressive function of Parkin and identified Parkin downregulation as a critica

43 ed to hyperlipidemia led to increased aortic Parkin and IL-6 levels, impaired mitochondrial function,

44 se results highlight the combined effects of Parkin and PGC-1alpha in the maintenance of mitochondria

45 cent research in murine models suggests that parkin and PINK1 deficiency leads to impaired mitophagy,

46 Together, parkin and PINK1 regulate the mitophagy pathway, which r

47 ion between various genetic factors, such as parkin and PINK1, in this disease.

48 itochondria involves the E3 ubiquitin ligase Parkin and PTEN-induced kinase 1 (PINK1), which cooperat

49 The physical and genetic interaction between Parkin and SLP-2 and the compensatory potential of SLP-2

50 hila studies showed a genetic interaction of Parkin and SLP-2, and further, tissue-specific or global

51 se toxins also induced the autophagic marker Parkin and the mitochondrial fission marker Dynamin-rela

52 These genes encode the E3 ubiquitin ligase parkin and the protein kinase PTEN-induced kinase 1 (PIN

53 These results offer a new link between Parkin and the serine synthesis pathway, and they bear t

54 spho-Parkin (Ser65) along with loss of total Parkin and total Drp1.

55 paring ubiquitinated proteins in hearts from Parkin(-/-) and Parkin transgenic mice identified the tr

56 disease-associated proteins alpha-Synuclein, Parkin, and Huntingtin (Htt).

57 issue homeostasis upon reduction of Pink1 or Parkin appears to result from reduction of age- and stre

58 mitochondria via mitophagy and mutations in Parkin are a major cause of early-onset Parkinson's dise

59 hat phenotypes associated with loss of Pink1/parkin are not universally due to aberrant activation of

60 Mutations in the E3 ubiquitin ligase parkin are the most common known cause of autosomal rece

61 Our results revealed PHGDH ubiquitination by Parkin as a crucial mechanism for PHGDH regulation that

62 Our findings suggest that enhancing Parkin-associated mitophagy and mitochondrial biogenesis

63 ne prevented the increase in aortic IL-6 and Parkin, attenuated mitochondrial dysfunction, and reduce

64 ce, while acute exercise activated BNIP3 and Parkin autophagy.

65 These findings demonstrate that the AMPK-Parkin axis negatively regulates necroptosis by inhibiti

66 Parkinson disease gene and tumor suppressor Parkin bound and ubiquitinated PHGDH.

67 that mitochondrial import was stimulated by Parkin, but not by disease-causing Parkin variants.

68 omain and ubiquitin are required to activate parkin by releasing the UBL domain, forming an extended

69 uor can quantify activation or inhibition of PARKIN by structural mutations.

70 function mutations in the ubiquitin ligase, parkin, cause autosomal recessive Parkinson's disease, t

71 cts naturally occurring activation states of PARKIN caused by Ser(65) phosphorylation (pPARKIN) and p

72 econd genewise association was found for the Parkin coding gene PRKN (formerly PARK2) where 7 rare va

73 argeted Parkin revealed that during hypoxia, Parkin contributes to both increased and decreased trans

74 Here we examined whether CUL9 and Parkin cooperate to promote optimal neuronal survival in

75 The Parkin-coregulated gene (PACRG), which encodes a protein

76 arkin together did not enhance the effect of Parkin deficiency alone.

77 l compartment and found a clear link between parkin deficiency and lysosomal alterations.

78 Parkin deficiency enhances inflammation and inflammation

79 Parkin deficiency in cancer cells stabilized PHGDH and a

80 enable mechanistic studies of the effect of parkin deficiency in human dopaminergic neurons.

81 Although transient parkin deficiency mildly impaired mitochondrial turnover

82 Parkin deficiency potentiates the RIPK1-RIPK3 interactio

83 on, and islet architecture were preserved in parkin-deficient beta cells and islets, suggesting that

84 irment of the autophagy-lysosomal pathway in parkin-deficient cells.

85 nal potential that warrants further study in Parkin-deficient human cancers.

86 stress induced by hydrogen peroxide or CCCP, parkin degradation also requires its association with ph

87 f HIPK2 and its kinase activity in promoting Parkin degradation via the proteasome-mediated mechanism

88 se 2 (HIPK2) and its kinase activity promote Parkin degradation via the proteasome-mediated pathway.

89 d mitochondrial turnover in beta cell lines, parkin deletion in primary beta cells yielded no deficit

90 SOD1 induced reductions in Miro1 levels were Parkin dependent.

91 pite significant understanding of both PINK1-Parkin-dependent and -independent mitochondrial quality

92 (PTEN)-induced Putative Kinase 1 (PINK1) and Parkin-dependent degradation of Miro1 and consequently s

93 Importantly, Tollip regulates Parkin-dependent endosomal trafficking of a discrete sub

94 transport of mitochondria by inducing PINK1/Parkin-dependent Miro1 degradation.

95 tion via modulation of redox homeostasis and Parkin-dependent mitochondrial clearance.

96 Our findings also suggest that targeting the parkin-dependent mitophagy pathway could be an effective

97 riggers, and identify numerous components of parkin-dependent mitophagy(1).

98 c or selective autophagic stimuli, including parkin-dependent mitophagy, and cells lacking all ATG8 p

99 Mdm2 facilitates and its knockdown reduces parkin-dependent mitophagy.

100 imination, in which these organelles undergo Parkin-dependent sequestration into Rab5-positive early

101 Mitochondrial stress promoted Parkin-dependent turnover of CCP1, and CCP1 and Parkin p

102 tochondria independently of parkin, enhances parkin-dependent ubiquitination of the outer mitochondri

103 cs to reveal the dynamics and specificity of Parkin-dependent ubiquitylation under endogenous express

104 RNA interference-mediated Parkin depletion attenuates CD44H cell generation.

105 Parkin depletion in cardiac HL-1 cells increased CHOP le

106 omal recessive Parkinson's disease (PD), and parkin depletion may play a role in sporadic PD.

107 First, we confirmed that PARKIN does not require an E2 enzyme for substrate ubiqu

108 d as a Parkin substrate and its turnover was Parkin-dose and proteasome-dependent.

109 uppressive function of Parkin and identified Parkin downregulation as a critical mechanism underlying

110 Parkin downregulation in breast cancer cells promotes me

111 r-activated receptor-gamma coactivator 1), a Parkin downstream target that can provide additional ben

112 r-activated receptor-gamma coactivator 1), a Parkin downstream target that can provide additional ben

113 f mitochondria-derived cargos independent of Parkin, Drp1, and autophagy.

114 PTEN-induced kinase 1 (PINK1) activity, and Parkin E3 ligase activity toward CDGSH iron sulfur domai

115 hPINK1 activates Parkin E3 ligase activity, involving phosphorylation of

116 RNAseq analysis revealed the PARKIN-encoding locus as a prime THAP11 target, and THAP

117 tes to damaged mitochondria independently of parkin, enhances parkin-dependent ubiquitination of the

118 l content and mitochondrial translocation of Parkin, essential in mitophagy.

119 tive mitochondria were evident from enhanced Parkin expression and mitochondrial proteome ubiquitinat

120 We found that CO induced Parkin expression in hepatocytes via the protein kinase

121 Parkin expression is frequently downregulated in many ty

122 Importantly, Parkin expression is inversely correlated with HIF-1alph

123 Furthermore, Parkin expression was inversely correlated with PHGDH ex

124 markers of cell cycle arrest, and decreased parkin expression.

125 liver injury by increasing hepatic HO-1 and Parkin expression.

126 ile dramatically increasing hepatic HO-1 and Parkin expression.

127 at these changes may contribute to a loss of parkin expression.

128 aces further emphasis on the significance of Parkin for the maintenance of mitochondrial function in

129 mitochondrial alterations caused by reduced Parkin function in these cells.

130 nduced cell death, whereas overexpression of parkin had the opposite effect.

131 To study whether Parkin has a role in vivo in the context of mitochondria

132 While parkin has been implicated in the regulation of mitophag

133 Neuroprotective activity of parkin has been linked to its critical role in the mitoc

134 Although parkin has been reported previously to control mitophagy

135 Parkin has been shown to participate in mitochondrial tu

136 Here, we demonstrate that Parkin has functions in the nucleus and that Parkinson's

137 In vivo, Parkin has significant protective effects on the surviva

138 unction mutations in the E3 ubiquitin ligase parkin have been implicated in the death of dopaminergic

139 text of mitochondrial damage, we knocked out Parkin in a mouse model in which the mitochondrial DNA i

140 ely assess the activity of the RBR E3 ligase PARKIN in a simple experimental setup and in real time u

141 genetic interactions between Sting and Pink1/parkin in Drosophila.

142 Here we show that parkin in inactivated through c-Abelson kinase phosphory

143 ondrial function and increased the levels of Parkin in the aortas of aged mice but not young mice.

144 rial quality control in vivo by knocking out Parkin in the PD-mito-PstI mouse (males), where the mito

145 through c-Abelson kinase phosphorylation of parkin in three alpha-synuclein-induced models of neurod

146 se results shed new light on the function of Parkin in vivo.

147 f parkin interacting substrate protein links parkin inactivation and alpha-synuclein in a common path

148 Whether parkin inactivation is a driver of neurodegeneration in

149 rtical neurons, co-expressing PGC-1alpha and Parkin increases the number of mitochondria, enhances ma

150 Further analysis uncovered that nuclear Parkin increases the transcriptional activity of ERRalph

151 engulfment (via TBK1 activation) in a PINK1-Parkin independent manner.

152 synuclein ubiquitination and clearance, in a parkin-independent manner.

153 ontaining protein-1 (FUNDC1), an effector of Parkin-independent mitophagy, also participates in cellu

154 These findings highlight that parkin-independent processes maintain beta cell and adip

155 PHB2 is required for Parkin-induced mitophagy in mammalian cells and for the

156 Parkin interacted with PHGDH and ubiquitinated PHGDH at

157 This results in the accumulation of parkin interacting substrate protein (zinc finger protei

158 induced neurodegeneration, since knockout of parkin interacting substrate protein attenuates the dege

159 Thus, suppression of parkin interacting substrate protein could be a potentia

160 ing multifunctional protein 2 with increased parkin interacting substrate protein levels playing a cr

161 Thus, accumulation of parkin interacting substrate protein links parkin inacti

162 Moreover, Parkin interactomes also involve signaling pathways and

163 recipitation confirmed that nuclear-targeted Parkin interacts with and ubiquitinates ERRalpha.

164 on endogenous proteins, we demonstrate that Parkin interacts with mitochondrial Stomatin-like protei

165 The E3 ubiquitin ligase parkin is a critical regulator of mitophagy and has been

166 a key regulator of SV proteostasis and that Parkin is a key E3 ligase in the autophagy-mediated clea

167 Parkin is a mostly cytosolic protein, but is rapidly rec

168 Accumulating evidence suggests that Parkin is a tumor suppressor, but the underlying mechani

169 Here we show that Parkin is an E3 ubiquitin ligase for hypoxia-inducible f

170 Parkin is an E3 ubiquitin ligase that is regulated by ub

171 Parkin is an E3 ubiquitin ligase well-known for facilita

172 Parkin is an E3 ubiquitin ligase, functioning in mitopha

173 Parkin is associated with autosomal recessive early-onse

174 The interaction between Tollip and Parkin is dependent on the ubiquitin-binding CUE domain

175 mitophagy, here we show that, surprisingly, parkin is dispensable for glucose homeostasis in both be

176 Additionally, Parkin is identified as a novel post-translational regul

177 Parkinson's disease, there is evidence that parkin is inactivated in sporadic Parkinson's disease.

178 , our experiments unexpectedly revealed that parkin is not an essential regulator of glucose toleranc

179 cient beta cells and islets, suggesting that parkin is not necessary for control of beta cell functio

180 Parkin is phosphorylated and activated by the cellular e

181 The E3 ligase Parkin is required for increased autophagy in Bassoon-de

182 onclude that Tollip, via an association with Parkin, is an essential coordinator to sort damaged mito

183 I is required and serves as both a PINK1 and Parkin kinase.

184 induced cell death when CHOP was depleted in Parkin knockdown cardiomyocytes.

185 Wild-type, Parkin knockout and MitoTimer-expressing mice were subje

186 rroborate these findings in vivo, we treated Parkin knockout mice with simvastatin for 2 wk.

187 he salutary effects of the drug were lost in Parkin knockout mice, implicating Parkin-mediated mitoph

188 24+/-0.005 in wild type and 0.176+/-0.018 in Parkin KO, P<0.05) in response to HFD feeding.

189 ciated with enhanced mitophagy and increased Parkin levels.

190 p97 was dispensable for Parkin ligase activity in iNeurons.

191 We find that L-DOPA causes parkin loss through both oxidative stress-independent an

192 ration in both sporadic and familial PD upon parkin loss-of-function remains unknown.

193 ions, providing one possible explanation why Parkin may be a tumor suppressor gene.

194 d for mitophagy, mutant MFN2 did not inhibit Parkin-mediated degradation, but instead had a dominant

195 FECD, intracellular oxidative stress induces Parkin-mediated mitochondrial fragmentation where endoge

196 mpairs the protective functions of the PINK1/parkin-mediated mitochondrial quality control.

197 in mammals, recent findings related to PINK1/Parkin-mediated mitophagy (which is the most well-studie

198 re lost in Parkin knockout mice, implicating Parkin-mediated mitophagy as part of its mechanism of ac

199 depolarized mitochondria reveals that PINK1/parkin-mediated mitophagy predominantly exploits mono- a

200 hondrial unfolded protein response and PINK1-Parkin-mediated mitophagy to mitigate proteotoxicity.

201 and downstream regulators of canonical PINK1/parkin-mediated mitophagy, alongside noncanonical PINK1/

202 s that are exacerbated by anomalies in PINK1/Parkin-mediated mitophagy, causing the accumulation of d

203 tensin-induced putative kinase 1 and blocks Parkin-mediated mitophagy, resulting in greater mitochon

204 51, an ER-Mito anchoring protein, suppresses Parkin-mediated mitophagy.

205 ifically on damaged mitochondria, triggering Parkin-mediated mitophagy.

206 ial stress and motility before activation of Parkin-mediated mitophagy.

207 of mitochondria function through regulating parkin-mediated mitophagy.

208 e to target HIPK2 in neuroprotection via the Parkin-mediated pathway.SIGNIFICANCE STATEMENT In this s

209 Here, we show that PHGDH is a substrate for Parkin-mediated ubiquitination and degradation.

210 Although the mechanism by which Parkin mediates mitophagy in a PINK1-dependent manner is

211 This review focuses on non-Parkin members such as HOIP/HOIL-1L (the only E3s known

212 estingly, this interaction is independent of Parkin mitochondrial recruitment and ligase activity but

213 ated mitophagy, alongside noncanonical PINK1/parkin mitophagy, in response to mitochondrial damage.

214 unprecedented quantitative landscape of the Parkin-modified ubiquitylome in iNeurons and reveals the

215 l overexpression of SLP-2 transgenes rescued parkin mutant phenotypes, in particular loss of dopamine

216 leus and that Parkinson's disease-associated Parkin mutants, ParkinR42P and ParkinG430D, are selectiv

217 cits or mitochondria disruption in the Pink1/parkin mutants.

218 d pluripotent stem cell-derived neurons from Parkin mutation carriers, showed decreased complex I act

219 lpha mutation and specific cancer-associated Parkin mutations largely abolish the functions of Parkin

220 assoon-deficient neurons as the knockdown of Parkin normalized autophagy and SV protein levels and re

221 Conversely, inactivation of Parkin not only accelerated tumor growth, but also sensi

222 of HO-1 and the mitophagy regulator protein Parkin on APAP-induced expression of the ER stress-assoc

223 Mfn2 protein, a key ubiquitylation target of Parkin on mitochondria.

224 We studied the role of Parkin on mitochondrial quality control in vivo by knock

225 h ubiquitin and the ubiquitin-like domain of Parkin on structurally protected Ser65 residues, trigger

226 We show that PINK1 recruits Parkin onto mitochondrial subdomains after actinonin-ind

227 SH-SY5Y cells with a stable knockdown of Parkin or SLP-2, as well as induced pluripotent stem cel

228 e-1)-, PDR-1 (Parkinson's disease-related-1; parkin)-, or DCT-1 (DAF-16/FOXO-controlled germline-tumo

229 Finally, we show that Parkin overexpression exacerbates, instead of ameliorati

230 ed that patients with BD had lower levels of Parkin, p62/SQSTM1 and LC3A and an upregulation of TSPO

231 Similarly to Parkin, PACRG promoted nuclear factor kappaB (NF-kappaB)

232 ived dopaminergic neurons from patients with parkin (PARK2) gene mutations compared to those from hea

233 ant brains had elevated auxilin (PARK19) and parkin (PARK2) levels.

234 Deletion of Parkin partially inhibited mitophagy, increased lipid ac

235 The PINK1/Parkin pathway has been described to play a central role

236 demonstrated the essential role of the PINK1-Parkin pathway in mitophagy induction in response to mit

237 hila revealed an essential role of the PINK1-Parkin pathway in mitophagy induction in vivo.

238 in homolog-induced putative kinase 1 (PINK1)-Parkin pathway is essential for the induction of mitopha

239 lves the PTEN-induced kinase 1/Parkin (Pink1/Parkin) pathway and autophagosomes labeled with the auto

240 kin-dependent turnover of CCP1, and CCP1 and Parkin physically interacted.

241 ntrol and involves the PTEN-induced kinase 1/Parkin (Pink1/Parkin) pathway and autophagosomes labeled

242 We analysed mutations in PRKN (parkin), PINK1, LRRK2 and SNCA in relation to age at sym

243 OS may act as a trigger for the induction of Parkin/PINK1-dependent mitophagy.

244 Parkin prevents the formation of the RIPK1-RIPK3 complex

245 s PTEN-induced putative kinase 1 (PINK1) and parkin (PRKN) in mediating mitochondrial degradation (mi

246 nction, shares a bidirectional promoter with Parkin (PRKN), which encodes an E3 ubiquitin ligase.

247 Mutations in PINK1 and Parkin/PRKN cause the degeneration of dopaminergic neuro

248 The lack of Parkin promoted earlier onset of dopaminergic neurodegen

249 Parkin promoted PHGDH degradation, suppressed serine syn

250 The E3 ubiquitin ligase Parkin promotes the degradation of damaged mitochondria

251 However, the mechanism that regulates Parkin protein level remains poorly understood.

252 The loss of HIPK2 leads to higher cytosolic Parkin protein levels at basal conditions and upon expos

253 HIPK2 increases cytosolic and mitochondrial Parkin protein levels under basal conditions and upon ex

254 ate the mechanisms by which stress decreases parkin protein levels using cultured neuronal cells and

255 an have neuroprotective effects by elevating Parkin protein levels.

256 The ubiquitin ligase Parkin, protein kinase PINK1, USP30 deubiquitylase, and

257 drial proteotoxicity and that PINK1 recruits Parkin proximal to focal misfolded aggregates of the mit

258 ted by various imaging methods in transgenic Parkin Q311(X)A mice and compared with those in healthy

259 r complete restoration of motor functions in Parkin Q311X(A) mice and improved brain tissue integrity

260 GDNF-transfected macrophages in a transgenic Parkin Q311X(A) mice with slow progression and mild brai

261 Parkin reconstitution rescued this phenotype and the con

262 Bay 11-7082, indicated that UBE2N modulates parkin recruitment and downstream events in the mitophag

263 crofluidics platform to assess the timing of parkin recruitment to depolarized mitochondria and its m

264 eloped a high-content imaging-based assay of parkin recruitment to mitochondria and screened both a d

265 lycogen synthase kinase 3, as a modulator of parkin recruitment.

266 cological compounds modulate PINK1-dependent parkin recruitment.

267 les for Parkin and demonstrates that nuclear Parkin regulates transcription of genes involved in mult

268 R sheets for degradation, analogous to PINK1-Parkin regulation during mitophagy.

269 hether Sting plays a conserved role in Pink1/parkin related pathology, we tested for genetic interact

270 ranslational level via induction of HO-1 and Parkin, respectively, and associated with decreases in r

271 erexpressing wild type or a nuclear-targeted Parkin revealed that during hypoxia, Parkin contributes

272 However, knowledge of Parkin's functions beyond mitophagy is still limited.

273 s that it requires both the kinase PINK1 and parkin's interaction with phosphorylated ubiquitin (phos

274 optimal glycemic control to prevent T2D, but parkin's role in preserving quality control of beta cell

275 PINK1 phosphorylation of serine 65 in parkin's UBL and serine 65 of ubiquitin fully activate u

276 evealed an accumulation of PINK1 and phospho-Parkin (Ser65) along with loss of total Parkin and total

277 Although the PINK1-Parkin signaling pathway is active in response to CCCP t

278 CHOP was identified as a Parkin substrate and its turnover was Parkin-dose and pr

279 down of the mitophagy-related genes Pink1 or Parkin suppresses the age-related loss of tissue homeost

280 ted receptor alpha (ERRalpha) as a potential Parkin target.

281 We observed that amino acids in Parkin targeted by nonsynonymous T1R-risk mutations were

282 quitylation kinetics of the vast majority of Parkin targets are unaffected, correlating with a modest

283 he deubiquitylase Usp7, the ubiquitin ligase Parkin, the cochaperone Bag6, and the protein phosphatas

284 ations in key mitophagy regulators PINK1 and Parkin to early-onset PD.

285 ad, loss of Drp1 enhances the recruitment of Parkin to fused mitochondrial networks and the rate of m

286 e kinase PINK1 is responsible for recruiting Parkin to mitochondria, but translocation of Parkin to t

287 tein quantity of PINK1 in the recruitment of Parkin to mitochondria.

288 Parkin to mitochondria, but translocation of Parkin to the nucleus occurs independently of PINK1.

289 n mutations largely abolish the functions of Parkin to ubiquitinate HIF-1alpha and inhibit cancer met

290 ovide additional enzymatic activities (e.g., Parkin) to proteasomes, but also increase their capacity

291 Our results show that the loss of Cul9 and Parkin together did not enhance the effect of Parkin def

292 ated proteins in hearts from Parkin(-/-) and Parkin transgenic mice identified the transcription fact

293 Further, Parkin translocates to the nucleus in response to hypoxi

294 nhibited the ROS upsurge and PINK1-dependent Parkin translocation to mitochondria in response to carb

295 ge-dependent anion channel 1 (VDAC1) induced Parkin translocation to mitochondria, presumably by stim

296 ochondrial import by the PINK1 kinase-driven Parkin ubiquitin ligase, which is dysfunctional in autos

297 volving phosphorylation of ubiquitin and the Parkin ubiquitin-like (Ubl) domain via as yet poorly und

298 Parkin ubiquitinates proteins on mitochondria that lost

299 ulated by Parkin, but not by disease-causing Parkin variants.

300 lation for mitophagy, mitochondria-localized parkin was severely reduced in control HFD-fed mouse hea