Vitamin K2 Is a Mitochondrial Electron Carrier That Rescues Pink1 Deficiency
@article{Vos2012VitaminKI, title={Vitamin K2 Is a Mitochondrial Electron Carrier That Rescues Pink1 Deficiency}, author={Melissa Vos and Giovanni Esposito and Janaka N. Edirisinghe and Sven Vilain and Dominik M Haddad and Jan R. Slabbaert and Stefanie Van Meensel and Onno Schaap and Bart de Strooper and Rangaswamy Meganathan and Vanessa Alexandra Morais and Patrik Verstreken}, journal={Science}, year={2012}, volume={336}, pages={1306 - 1310} }
Keeping Mitochondria in the Pink Pink1 is a mitochondrial kinase, and loss of Pink1 function in flies and mice results in the accumulation of inefficient mitochondria. In a screen for modifiers of the Parkinson-associated gene, pink1, Vos et al. (p. 1306, published online 10 May; see the Perspective by Bhalerao and Clandinin) identified the fruit fly homolog of UBIAD1, “Heix.” UBIAD1 was localized in mitochondria and was able to convert vitamin K1 into vitamin K2/menaquinone (MK-n, n the number…
286 Citations
PINK1 Loss-of-Function Mutations Affect Mitochondrial Complex I Activity via NdufA10 Ubiquinone Uncoupling
- BiologyScience
- 2014
Phosphomimetic NdufA10 reversed Pink1 deficits in mouse knockout cells and rescued mitochondrial depolarization and synaptic transmission defects in pinkB9-null mutant Drosophila.
Cardiolipin promotes electron transport between ubiquinone and complex I to rescue PINK1 deficiency
- BiologyThe Journal of cell biology
- 2017
It is found that partial genetic and pharmacological inhibition of fatty acid synthase (FASN) suppresses toxicity induced by PINK1 deficiency in flies, mouse cells, patient-derived fibroblasts, and induced pluripotent stem cell–derived dopaminergic neurons.
Mitochondrial Regulation by PINK 1-Parkin Signaling
- Biology
- 2014
The roles of PINK1-Parkin signaling for mitochondrial maintenance and how the failure of this signaling leads to neurodegeneration are discussed.
Mitochondrial Regulation by PINK1-Parkin Signaling
- Biology
- 2012
The roles of PINK1-Parkin signaling for mitochondrial maintenance and how the failure of this signaling leads to neurodegeneration are discussed.
Beyond mitophagy: cytosolic PINK1 as a messenger of mitochondrial health.
- BiologyAntioxidants & redox signaling
- 2015
A working hypothesis is proposed that PINK1 is released by functional mitochondria as a signal to coordinate cell growth and differentiation in response to mitochondrial status, and may offer novel insights into howfunctional mitochondria communicate their status with the rest of the cell.
A Dimeric PINK1-containing Complex on Depolarized Mitochondria Stimulates Parkin Recruitment*
- Biology, ChemistryThe Journal of Biological Chemistry
- 2013
Formation of the complex containing dyadic PINK1 is an important step for Parkin recruitment onto damaged mitochondria and is correlated with intermolecular phosphorylation of Pink1.
The mitochondrial kinase PINK1: functions beyond mitophagy
- BiologyJournal of neurochemistry
- 2016
Mounting evidence indicates that PINK1 has additional functions, for example, in regulating complex I activity and maintaining neuronal viability in response to stress.
JCB_201511044 695..708
- Biology
- 2017
It is found that partial genetic and pharmacological inhibition of fatty acid synthase (FASN) suppresses toxicity induced by PINK1 deficiency in flies, mouse cells, patient-derived fibroblasts, and induced pluripotent stem cell–derived dopaminergic neurons.
The Complex I Subunit NDUFA10 Selectively Rescues Drosophila pink1 Mutants through a Mechanism Independent of Mitophagy
- BiologyPLoS genetics
- 2014
The results indicate that the in vivo rescue of pink1 mutants is due to restoring CI activity rather than promoting mitophagy, and support the emerging view that PINK1 plays a role in regulating CI activity separate from its role with Parkin inMitophagy.
Enhancing NAD+ salvage metabolism is neuroprotective in a PINK1 model of Parkinson's disease
- BiologyBiology Open
- 2016
It is shown that a diet supplemented with the NAD+ precursor nicotinamide rescued mitochondrial defects and protected neurons from degeneration and a mutation of Parp improved mitochondrial function and was neuroprotective in the pink1 mutants.
References
SHOWING 1-10 OF 51 REFERENCES
The Yeast Complex I Equivalent NADH Dehydrogenase Rescues pink1 Mutants
- BiologyPLoS genetics
- 2012
A central role for Complex I dysfunction in pink1-associated defects is indicated, and genetic analyses with heterologous ETC enzymes suggest that Ndi1p-dependent NADH dehydrogenase activity largely acts downstream of, or in parallel to, Pink1 but upstream of Parkin and mitochondrial remodeling.
Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin
- BiologyNature
- 2006
Removal of Drosophila PINK1 homologue function results in male sterility, apoptotic muscle degeneration, defects in mitochondrial morphology and increased sensitivity to multiple stresses including oxidative stress, which underscores the importance of mitochondrial dysfunction as a central mechanism of Parkinson's disease pathogenesis.
The Parkinson's disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila
- BiologyProceedings of the National Academy of Sciences
- 2008
Interactions between pink1 and parkin are likely not core components of the drp1-mediated mitochondrial fission machinery, and modification of fusion and fission may represent a novel therapeutic strategy for Parkinson's disease.
Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin
- BiologyNature
- 2006
The genetic evidence clearly establishes that Parkin and PINK1 act in a common pathway in maintaining mitochondrial integrity and function in both muscles and dopaminergic neurons.
Drosophila sbo regulates lifespan through its function in the synthesis of coenzyme Q in vivo.
- Biology, ChemistryJournal of genetics and genomics = Yi chuan xue bao
- 2011
Parkin negatively regulates JNK pathway in the dopaminergic neurons of Drosophila.
- Biology, PsychologyProceedings of the National Academy of Sciences of the United States of America
- 2005
It is suggested that loss of Parkin function up-regulates the JNK signaling pathway, which may contribute to the vulnerability of dopaminergic neurons in Drosophila parkin mutants and perhaps autosomal recessive juvenile parkinsonism patients.
Synaptic Mitochondria Are Critical for Mobilization of Reserve Pool Vesicles at Drosophila Neuromuscular Junctions
- BiologyNeuron
- 2005
Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme
- BiologyNature
- 2010
The results show that UBIAD1 is a human MK-4 biosynthetic enzyme, and this identification will permit more effective decisions to be made about vitamin K intake and bone health.
UBIAD1 Mutation Alters a Mitochondrial Prenyltransferase to Cause Schnyder Corneal Dystrophy
- Biology, MedicinePloS one
- 2010
Accumulating evidence from the SCD familial mutation spectrum, protein homology across species, and molecular modeling suggest that protein function is likely down-regulated by SCD mutations.
Paraquat induces oxidative stress and neuronal cell death; neuroprotection by water-soluble Coenzyme Q10.
- BiologyToxicology and applied pharmacology
- 2004