General Information:

Id: 543
Diseases: Parkinson disease
Homo sapiens
BTO:0000567 HeLa cell; BTO:0000793 SH-SY5Y cell
article
Reference: Geisler S et al.(2010) PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1 Nat. Cell Biol. 12: 119-131 [PMID: 20098416]

Interaction Information:

Comment Treatment with the uncoupler CCCP induced complete translocation of transfected Parkin from the cytoplasm to depolarized mitochondria. Parkin localized to mitochondria induces mitophagy.
Formal Description
Interaction-ID: 2744

drug/chemical compound

CCCP

increases_transport of

gene/protein

PARK2

into mitochondria
Comment Parkin mutants K211N, T240R and G430D retained their cytosolic distribution and failed to translocate to mitochondria after CCCP treatment of the cells. As a result, autophagic clearance of depolarized mitochondria is blocked.
Formal Description
Interaction-ID: 2745

drug/chemical compound

CCCP

NOT increases_transport of

gene/protein mutant

PARK2-p.K211N

into mitochondria
Comment Parkin mutants K211N, T240R and G430D retained their cytosolic distribution and failed to translocate to mitochondria after CCCP treatment of the cells. As a result, autophagic clearance of depolarized mitochondria is blocked.
Formal Description
Interaction-ID: 2746

drug/chemical compound

CCCP

NOT increases_transport of

gene/protein mutant

PARK2-p.T240R

into mitochondria
Comment Parkin mutants K211N, T240R and G430D retained their cytosolic distribution and failed to translocate to mitochondria after CCCP treatment of the cells. As a result, autophagic clearance of depolarized mitochondria is blocked.
Formal Description
Interaction-ID: 2747

drug/chemical compound

CCCP

NOT increases_transport of

gene/protein mutant

PARK2-p.G430D

into mitochondria
Comment CCCP induces depolarization of the mitochondrial membrane resulting in damaged mitochondria which are usually sequestered by mitophagy.
Formal Description
Interaction-ID: 2748

drug/chemical compound

CCCP

increases_activity of

Comment CCCP induces depolarization of the mitochondrial membrane resulting in damaged mitochondria which are usually sequestered by mitophagy.
Formal Description
Interaction-ID: 2749

increases_activity of

Comment PD-associated insoluble Parkin mutants C212Y, C289G, C418R and C441R do not translocate to damaged mitochondria and do not induce mitochondrial clearance after CCCP treatment.
Formal Description
Interaction-ID: 2777

drug/chemical compound

CCCP

NOT increases_transport of

gene/protein mutant

PARK2-p.C212Y

into mitochondria
Comment Treatment with the uncoupler CCCP induced complete translocation of transfected Parkin from the cytoplasm to depolarized mitochondria. Parkin localized to mitochondria induces mitophagy.
Formal Description
Interaction-ID: 2785

gene/protein

PARK2

increases_activity of

if Parkin is localized in mitochondria
Comment Parkin mutants K211N, T240R and G430D retained their cytosolic distribution and failed to translocate to mitochondria after CCCP treatment of the cells. As a result, autophagic clearance of depolarized mitochondria is blocked.
Formal Description
Interaction-ID: 2788

gene/protein mutant

PARK2-p.K211N

NOT increases_activity of

after CCCP treatment
Comment Parkin mutants K211N, T240R and G430D retained their cytosolic distribution and failed to translocate to mitochondria after CCCP treatment of the cells. As a result, autophagic clearance of depolarized mitochondria is blocked.
Formal Description
Interaction-ID: 2789

gene/protein mutant

PARK2-p.T240R

NOT increases_activity of

after CCCP treatment
Comment Parkin mutants K211N, T240R and G430D retained their cytosolic distribution and failed to translocate to mitochondria after CCCP treatment of the cells. As a result, autophagic clearance of depolarized mitochondria is blocked.
Formal Description
Interaction-ID: 2790

gene/protein mutant

PARK2-p.G430D

NOT increases_activity of

after CCCP treatment
Comment PD-associated insoluble Parkin mutants C212Y, C289G, C418R and C441R do not translocate to damaged mitochondria and do not induce mitochondrial clearance after CCCP treatment.
Formal Description
Interaction-ID: 2791

drug/chemical compound

CCCP

NOT increases_transport of

gene/protein mutant

PARK2-p.C289G

into mitochondria
Comment PD-associated insoluble Parkin mutants C212Y, C289G, C418R and C441R do not translocate to damaged mitochondria and do not induce mitochondrial clearance after CCCP treatment.
Formal Description
Interaction-ID: 2792

drug/chemical compound

CCCP

NOT increases_transport of

gene/protein mutant

PARK2-p.C418R

into mitochondria
Comment PD-associated insoluble Parkin mutants C212Y, C289G, C418R and C441R do not translocate to damaged mitochondria and do not induce mitochondrial clearance after CCCP treatment.
Formal Description
Interaction-ID: 2793

drug/chemical compound

CCCP

NOT increases_transport of

gene/protein mutant

PARK2-p.C441R

into mitochondria
Comment PD-associated insoluble Parkin mutants C212Y, C289G, C418R and C441R do not translocate to damaged mitochondria and do not induce mitochondrial clearance after CCCP treatment.
Formal Description
Interaction-ID: 2794

gene/protein mutant

PARK2-p.C212Y

NOT increases_activity of

after CCCP treatment
Comment PD-associated insoluble Parkin mutants C212Y, C289G, C418R and C441R do not translocate to damaged mitochondria and do not induce mitochondrial clearance after CCCP treatment.
Formal Description
Interaction-ID: 2796

gene/protein mutant

PARK2-p.C289G

NOT increases_activity of

after CCCP treatment
Comment PD-associated insoluble Parkin mutants C212Y, C289G, C418R and C441R do not translocate to damaged mitochondria and do not induce mitochondrial clearance after CCCP treatment.
Formal Description
Interaction-ID: 2797

gene/protein mutant

PARK2-p.C418R

NOT increases_activity of

after CCCP treatment
Comment PD-associated insoluble Parkin mutants C212Y, C289G, C418R and C441R do not translocate to damaged mitochondria and do not induce mitochondrial clearance after CCCP treatment.
Formal Description
Interaction-ID: 2798

gene/protein mutant

PARK2-p.C441R

NOT increases_activity of

after CCCP treatment
Comment Soluble Parkin mutants K161N and R275W were recruited to mitochondria after CCCP treatment and resulted in mitochondrial clustering, similarly to wild-type Parkin. However, K161N and R275W failed to clear sequestered mitochondria.
Formal Description
Interaction-ID: 2801

drug/chemical compound

CCCP

increases_transport of

gene/protein mutant

PARK2-p.K161N

into mitochondria
Comment Soluble Parkin mutants K161N and R275W were recruited to mitochondria after CCCP treatment and resulted in mitochondrial clustering, similarly to wild-type Parkin. However, K161N and R275W failed to clear sequestered mitochondria.
Formal Description
Interaction-ID: 2802

drug/chemical compound

CCCP

increases_transport of

gene/protein mutant

PARK2-p.R275W

into mitochondria
Comment Soluble Parkin mutants K161N and R275W were recruited to mitochondria after CCCP treatment and resulted in mitochondrial clustering, similarly to wild-type Parkin. However, K161N and R275W failed to clear sequestered mitochondria.
Formal Description
Interaction-ID: 2804

gene/protein mutant

PARK2-p.K161N

NOT increases_activity of

after CCCP treatment
Comment Soluble Parkin mutants K161N and R275W were recruited to mitochondria after CCCP treatment and resulted in mitochondrial clustering, similarly to wild-type Parkin. However, K161N and R275W failed to clear sequestered mitochondria.
Formal Description
Interaction-ID: 2805

gene/protein mutant

PARK2-p.R275W

NOT increases_activity of

after CCCP treatment
Comment Parkin mutants P37L, R42P, R256C, G328E and R334C were rapidly recruited to mitochondria and facilitated mitochondrial degradation within 24 h, similarly to wild-type Parkin.
Formal Description
Interaction-ID: 2806

drug/chemical compound

CCCP

increases_transport of

gene/protein mutant

PARK2-p.P37L

into mitochondria
Comment Parkin mutants P37L, R42P, R256C, G328E and R334C were rapidly recruited to mitochondria and facilitated mitochondrial degradation within 24 h, similarly to wild-type Parkin.
Formal Description
Interaction-ID: 2807

drug/chemical compound

CCCP

increases_transport of

gene/protein mutant

PARK2-p.R42P

into mitochondria
Comment Parkin mutants P37L, R42P, R256C, G328E and R334C were rapidly recruited to mitochondria and facilitated mitochondrial degradation within 24 h, similarly to wild-type Parkin.
Formal Description
Interaction-ID: 2808

drug/chemical compound

CCCP

increases_transport of

gene/protein mutant

PARK2-p.R256C

into mitochondria
Comment Parkin mutants P37L, R42P, R256C, G328E and R334C were rapidly recruited to mitochondria and facilitated mitochondrial degradation within 24 h, similarly to wild-type Parkin.
Formal Description
Interaction-ID: 2809

drug/chemical compound

CCCP

increases_transport of

gene/protein mutant

PARK2-p.G328E

into mitochondria
Comment Parkin mutants P37L, R42P, R256C, G328E and R334C were rapidly recruited to mitochondria and facilitated mitochondrial degradation within 24 h, similarly to wild-type Parkin.
Formal Description
Interaction-ID: 2810

drug/chemical compound

CCCP

increases_transport of

gene/protein mutant

PARK2-p.R334C

into mitochondria
Comment Parkin mutants P37L, R42P, R256C, G328E and R334C were rapidly recruited to mitochondria and facilitated mitochondrial degradation within 24 h, similarly to wild-type Parkin.
Formal Description
Interaction-ID: 2811

gene/protein mutant

PARK2-p.P37L

increases_activity of

after CCCP treatment
Comment Parkin mutants P37L, R42P, R256C, G328E and R334C were rapidly recruited to mitochondria and facilitated mitochondrial degradation within 24 h, similarly to wild-type Parkin.
Formal Description
Interaction-ID: 2812

gene/protein mutant

PARK2-p.R42P

increases_activity of

after CCCP treatment
Comment Parkin mutants P37L, R42P, R256C, G328E and R334C were rapidly recruited to mitochondria and facilitated mitochondrial degradation within 24 h, similarly to wild-type Parkin.
Formal Description
Interaction-ID: 2813

gene/protein mutant

PARK2-p.R256C

increases_activity of

after CCCP treatment
Comment Parkin mutants P37L, R42P, R256C, G328E and R334C were rapidly recruited to mitochondria and facilitated mitochondrial degradation within 24 h, similarly to wild-type Parkin.
Formal Description
Interaction-ID: 2814

gene/protein mutant

PARK2-p.G328E

increases_activity of

after CCCP treatment
Comment Parkin mutants P37L, R42P, R256C, G328E and R334C were rapidly recruited to mitochondria and facilitated mitochondrial degradation within 24 h, similarly to wild-type Parkin.
Formal Description
Interaction-ID: 2815

gene/protein mutant

PARK2-p.R334C

increases_activity of

after CCCP treatment
Comment PINK1 knockdown significantly abolished Parkin recruitment to mitochondria after 2h of CCCP treatment as well as mitophagic clearance within 24 h.
Formal Description
Interaction-ID: 2824

gene/protein

PINK1

affects transport of

gene/protein

PARK2

into mitochondria; after CCCP treatment
Comment PINK1 knockdown significantly abolished Parkin recruitment to mitochondria after 2h of CCCP treatment as well as mitophagic clearance within 24 h.
Formal Description
Interaction-ID: 2827

gene/protein

PINK1

affects_activity of

after CCCP treatment
Comment Knockdown of p62 had no influence on mitochondrial translocation of Parkin, but completely blocks final clearance of damaged mitochondria.
Formal Description
Interaction-ID: 2847

gene/protein

SQSTM1

increases_activity of

Comment VDAC1 is ubiquitylated in a Parkin-dependent manner after CCCP treatment. None of the analysed pathogenic Parkin mutants were able to modify VDAC1.
Formal Description
Interaction-ID: 2850

gene/protein

PARK2

increases_ubiquitination/sumoylation of

gene/protein

VDAC1

after CCCP treatment
Drugbank entries Show/Hide entries for VDAC1
Comment VDAC1 is ubiquitylated in a Parkin-dependent manner after CCCP treatment. None of the analysed pathogenic Parkin mutants were able to modify VDAC1.
Formal Description
Interaction-ID: 2853

gene/protein mutant

PARK2-p.K161N

NOT increases_ubiquitination/sumoylation of

gene/protein

VDAC1

after CCCP treatment
Drugbank entries Show/Hide entries for VDAC1
Comment VDAC1 is ubiquitylated in a Parkin-dependent manner after CCCP treatment. None of the analysed pathogenic Parkin mutants were able to modify VDAC1.
Formal Description
Interaction-ID: 2854

gene/protein mutant

PARK2-p.K211N

NOT increases_ubiquitination/sumoylation of

gene/protein

VDAC1

after CCCP treatment
Drugbank entries Show/Hide entries for VDAC1
Comment VDAC1 is ubiquitylated in a Parkin-dependent manner after CCCP treatment. None of the analysed pathogenic Parkin mutants were able to modify VDAC1.
Formal Description
Interaction-ID: 2855

gene/protein mutant

PARK2-p.R275W

NOT increases_ubiquitination/sumoylation of

gene/protein

VDAC1

after CCCP treatment
Drugbank entries Show/Hide entries for VDAC1
Comment VDAC1 is ubiquitylated in a Parkin-dependent manner after CCCP treatment. None of the analysed pathogenic Parkin mutants were able to modify VDAC1.
Formal Description
Interaction-ID: 2856

gene/protein mutant

PARK2-p.G430D

NOT increases_ubiquitination/sumoylation of

gene/protein

VDAC1

after CCCP treatment
Drugbank entries Show/Hide entries for VDAC1
Comment Partial silencing of VDAC1 resulted in significantly reduced translocation of Parkin from the cytosol to damaged mitochondria after 2 h of CCCP treatment. After 24 h of CCCP treatment, partial knockdown of VDAC1 also significantly prevented mitochondrial clearance.
Formal Description
Interaction-ID: 2857

gene/protein

VDAC1

affects transport of

gene/protein

PARK2

into mitochondria; after CCCP treatment
Drugbank entries Show/Hide entries for VDAC1
Comment Partial silencing of VDAC1 resulted in significantly reduced translocation of Parkin from the cytosol to damaged mitochondria after 2 h of CCCP treatment. After 24 h of CCCP treatment, partial knockdown of VDAC1 also significantly prevented mitochondrial clearance.
Formal Description
Interaction-ID: 2858

gene/protein

VDAC1

affects_activity of

after CCCP treatment
Drugbank entries Show/Hide entries for VDAC1
Comment Silencing of TRAP1 had no effect on Parkin translocation or on mitochondrial clearance.
Formal Description
Interaction-ID: 2859

gene/protein

TRAP1

NOT affects transport of

gene/protein

PARK2

into mitochondria; after CCCP treatment