The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Pink1 Forms a Multiprotein Complex with Miro and Milton, Linking Pink1 Function to Mitochondrial Trafficking
Open accessAbstract
Recessive mutations in Pink1 lead to a selective degeneration of dopaminergic neurons in the substantia nigra that is characteristic of Parkinson disease. Pink1 is a kinase that is targeted in part to mitochondria, and loss of Pink1 function can alter mitochondrial morphology and dynamics, thus supporting a link between mitochondrial dysfunction and Parkinson disease etiology. Here, we report the unbiased identification and confirmation of a mitochondrial multiprotein complex that contains Pink1, the atypical GTPase Miro, and the adaptor protein Milton. Our screen also identified an interaction between Pink1 and Mitofilin. Based on previously established functions for Miro and Milton in the trafficking of mitochondria along microtubules, we postulate here a role for Pink1 in mitochondrial trafficking. Using subcellular fractionation, we show that the overexpression of Miro and Milton, both of which are known to reside at the outer mitochondrial membrane, increases the mitochondrial Pink1 pool, suggesting a function of Pink1 at the outer membrane. Further, we document that Pink1 expressed without a mitochondrial targeting sequence can still be targeted to a mitochondria-enriched subcellular fraction via Miro and Milton. The latter finding is important for the interpretation of a previously reported protective effect of Pink1 expressed without a mitochondrial targeting sequence. Finally, we find that Miro and Milton expression suppresses altered mitochondrial morphology induced by loss of Pink1 function in cell culture. Our findings suggest that Pink1 functions in the trafficking of mitochondria in cells.
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Cites
Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1
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Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin
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Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin
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PINK1 Protects against Oxidative Stress by Phosphorylating Mitochondrial Chaperone TRAP1
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PINK1 Is Selectively Stabilized on Impaired Mitochondria to Activate Parkin
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Self-citationPINK1-dependent recruitment of Parkin to mitochondria in mitophagy
Vives-Bauza, C., Zhou, C., Huang, Y., Cui, M., de Vries, R. L. A., Kim, J., May, J., Tocilescu, M. A., Liu, W., Ko, H. S., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911187107 · Cited by 1,616
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Mitochondrial dysfunction in Parkinson's disease
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Mitochondria: The Next (Neurode)Generation
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Mitochondrial Trafficking in Neurons
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“1 vector with a CMV promoter (Weihofen et al., 2009), mt-DsRed with a CMV promoter (Takara Bio Inc.), mt-GFP in the pShooter vector with a CMV promoter (gift of M. Haigis, Harvard Medical School, Boston, MA), pEGFP-N1 with a CMV promoter (Takara Bio Inc.), pKillerRed-dMito with a CMV promoter…”
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The Parkinson-associated protein PINK1 interacts with Beclin1 and promotes autophagy
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Depletion of PINK1 affects mitochondrial metabolism, calcium homeostasis and energy maintenance
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Inter and Intracellular mitochondrial trafficking in health and disease
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Metadata
- Authors
- Weihofen, A., Thomas, K. J., Ostaszewski, B. L., Cookson, M. R., & Selkoe, D. J.
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2009-01-20
- Volume
- 48
- Issue
- 9
- Pages
- 2045-2052
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- OpenAlex
- W2012014117
- Cited by
- 290
- References
- 7
- FWCI
- 18.94
- Type
- journal article
- Language
- en
- Open access
- green
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