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The Enzymatic Core of the Parkinson’s Disease-Associated Protein LRRK2 Impairs Mitochondrial Biogenesis in Aging Yeast

Overview of attention for article published in Frontiers in Molecular Neuroscience, June 2018
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  • Good Attention Score compared to outputs of the same age (65th percentile)
  • Good Attention Score compared to outputs of the same age and source (74th percentile)

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Title
The Enzymatic Core of the Parkinson’s Disease-Associated Protein LRRK2 Impairs Mitochondrial Biogenesis in Aging Yeast
Published in
Frontiers in Molecular Neuroscience, June 2018
DOI 10.3389/fnmol.2018.00205
Pubmed ID
Authors

Andreas Aufschnaiter, Verena Kohler, Corvin Walter, Sergi Tosal-Castano, Lukas Habernig, Heimo Wolinski, Walter Keller, F.-Nora Vögtle, Sabrina Büttner

Abstract

Mitochondrial dysfunction is a prominent trait of cellular decline during aging and intimately linked to neuronal degeneration during Parkinson's disease (PD). Various proteins associated with PD have been shown to differentially impact mitochondrial dynamics, quality control and function, including the leucine-rich repeat kinase 2 (LRRK2). Here, we demonstrate that high levels of the enzymatic core of human LRRK2, harboring GTPase as well as kinase activity, decreases mitochondrial mass via an impairment of mitochondrial biogenesis in aging yeast. We link mitochondrial depletion to a global downregulation of mitochondria-related gene transcripts and show that this catalytic core of LRRK2 localizes to mitochondria and selectively compromises respiratory chain complex IV formation. With progressing cellular age, this culminates in dissipation of mitochondrial transmembrane potential, decreased respiratory capacity, ATP depletion and generation of reactive oxygen species. Ultimately, the collapse of the mitochondrial network results in cell death. A point mutation in LRRK2 that increases the intrinsic GTPase activity diminishes mitochondrial impairment and consequently provides cytoprotection. In sum, we report that a downregulation of mitochondrial biogenesis rather than excessive degradation of mitochondria underlies the reduction of mitochondrial abundance induced by the enzymatic core of LRRK2 in aging yeast cells. Thus, our data provide a novel perspective for deciphering the causative mechanisms of LRRK2-associated PD pathology.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 42 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 17%
Researcher 7 17%
Student > Master 6 14%
Student > Bachelor 3 7%
Professor 3 7%
Other 8 19%
Unknown 8 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 14 33%
Agricultural and Biological Sciences 5 12%
Neuroscience 5 12%
Medicine and Dentistry 3 7%
Psychology 1 2%
Other 2 5%
Unknown 12 29%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 July 2018.
All research outputs
#7,581,759
of 26,456,908 outputs
Outputs from Frontiers in Molecular Neuroscience
#1,055
of 3,439 outputs
Outputs of similar age
#118,767
of 344,733 outputs
Outputs of similar age from Frontiers in Molecular Neuroscience
#29
of 113 outputs
Altmetric has tracked 26,456,908 research outputs across all sources so far. This one has received more attention than most of these and is in the 71st percentile.
So far Altmetric has tracked 3,439 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.6. This one has gotten more attention than average, scoring higher than 69% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 344,733 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 65% of its contemporaries.
We're also able to compare this research output to 113 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 74% of its contemporaries.