GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:20194754

From GONUTS
Jump to: navigation, search
Citation

Ziviani, E, Tao, RN and Whitworth, AJ (2010) Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin. Proc. Natl. Acad. Sci. U.S.A. 107:5018-23

Abstract

Loss of the E3 ubiquitin ligase Parkin causes early onset Parkinson's disease, a neurodegenerative disorder of unknown etiology. Parkin has been linked to multiple cellular processes including protein degradation, mitochondrial homeostasis, and autophagy; however, its precise role in pathogenesis is unclear. Recent evidence suggests that Parkin is recruited to damaged mitochondria, possibly affecting mitochondrial fission and/or fusion, to mediate their autophagic turnover. The precise mechanism of recruitment and the ubiquitination target are unclear. Here we show in Drosophila cells that PINK1 is required to recruit Parkin to dysfunctional mitochondria and promote their degradation. Furthermore, PINK1 and Parkin mediate the ubiquitination of the profusion factor Mfn on the outer surface of mitochondria. Loss of Drosophila PINK1 or parkin causes an increase in Mfn abundance in vivo and concomitant elongation of mitochondria. These findings provide a molecular mechanism by which the PINK1/Parkin pathway affects mitochondrial fission/fusion as suggested by previous genetic interaction studies. We hypothesize that Mfn ubiquitination may provide a mechanism by which terminally damaged mitochondria are labeled and sequestered for degradation by autophagy.

Links

PubMed PMC2841909 Online version:10.1073/pnas.0913485107

Keywords

Animals; Autophagy; Drosophila Proteins/metabolism; Drosophila melanogaster/cytology; Drosophila melanogaster/enzymology; Gene Knockdown Techniques; Membrane Proteins/metabolism; Mitochondria/enzymology; Mutation/genetics; Protein Transport; Protein-Serine-Threonine Kinases/metabolism; Ubiquitin-Protein Ligases; Ubiquitination

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:A0A0B4LF33

involved_in

GO:0010636: positive regulation of mitochondrial fusion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:A0A0B4LFB8

involved_in

GO:0010636: positive regulation of mitochondrial fusion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:A0A0B4LGF5

involved_in

GO:0010636: positive regulation of mitochondrial fusion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:FIS1

involved_in

GO:0090141: positive regulation of mitochondrial fission

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:PINK1

involved_in

GO:0000422: autophagy of mitochondrion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:PINK1

involved_in

GO:0010637: negative regulation of mitochondrial fusion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:PINK1

involved_in

GO:0006511: ubiquitin-dependent protein catabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:PINK1

involved_in

GO:0090141: positive regulation of mitochondrial fission

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:PRKN

involved_in

GO:0000422: autophagy of mitochondrion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:PRKN

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:PRKN

involved_in

GO:0010637: negative regulation of mitochondrial fusion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:PRKN

involved_in

GO:0006511: ubiquitin-dependent protein catabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:PRKN

colocalizes_with

GO:0005739: mitochondrion

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:PRKN

involved_in

GO:0090141: positive regulation of mitochondrial fission

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:MARF

involved_in

GO:0010636: positive regulation of mitochondrial fusion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q8IHG0

involved_in

GO:0090141: positive regulation of mitochondrial fission

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q8T9L0

involved_in

GO:0090141: positive regulation of mitochondrial fission

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q95U20

involved_in

GO:0010636: positive regulation of mitochondrial fusion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VQE0

involved_in

GO:0090141: positive regulation of mitochondrial fission

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q961J3

involved_in

GO:0000422: autophagy of mitochondrion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q961J3

involved_in

GO:0006511: ubiquitin-dependent protein catabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q961J3

involved_in

GO:0010637: negative regulation of mitochondrial fusion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q961J3

involved_in

GO:0090141: positive regulation of mitochondrial fission

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q0KHV6

involved_in

GO:0090141: positive regulation of mitochondrial fission

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q0KHV6

involved_in

GO:0010637: negative regulation of mitochondrial fusion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q0KHV6

involved_in

GO:0006511: ubiquitin-dependent protein catabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q0KHV6

involved_in

GO:0000422: autophagy of mitochondrion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q7KTX7

involved_in

GO:0006511: ubiquitin-dependent protein catabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q7KTX7

colocalizes_with

GO:0005739: mitochondrion

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:Q7KTX7

involved_in

GO:0010637: negative regulation of mitochondrial fusion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q7KTX7

involved_in

GO:0090141: positive regulation of mitochondrial fission

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q7KTX7

involved_in

GO:0000422: autophagy of mitochondrion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q7KTX7

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:Q7KTX7

GO:0044743: intracellular protein transmembrane import

ECO:0000316:

UniProtKB:Q0KHV6


P

Figure 2 shows PINK1 is required for Parkin translocation

complete
CACAO 10621

DROME:Q7KTX7

GO:0031398: positive regulation of protein ubiquitination

ECO:0000314:

P

Figure 4 shows parkin overexpression can cause mfn ubiquitination in the absense of PINK1

complete
CACAO 10622

DROME:Q7KTX7

GO:0090141: positive regulation of mitochondrial fission

ECO:0000316:

UniProtKB:Q0KHV6


P

Figure 1 shows Parkin and PINK1 activity promotes mitochondrial fission

complete
CACAO 10623

DROME:Q7KTX7

GO:0010637: negative regulation of mitochondrial fusion

ECO:0000316:

UniProtKB:Q0KHV6


P

Figure 1 shows Parkin and PINK1 activity inhibits mitochondrial fusion

complete
CACAO 10624

DROME:A1Z9N0

involved_in

GO:0010636: positive regulation of mitochondrial fusion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

See Help:References for how to manage references in GONUTS.