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  4. Cerebellar Ataxia and Coenzyme Q Deficiency through Loss of Unorthodox Kinase Activity
 
research article

Cerebellar Ataxia and Coenzyme Q Deficiency through Loss of Unorthodox Kinase Activity

Stefely, Jonathan A.
•
Licitra, Floriana
•
Laredj, Leila
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2016
Molecular Cell

The UbiB protein kinase-like (PKL) family is widespread, comprising one-quarter of microbial PKLs and five human homologs, yet its biochemical activities remain obscure. COQ8A (ADCK3) is a mammalian UbiB protein associated with ubiquinone (CoQ) biosynthesis and an ataxia (ARCA2) through unclear means. We show that mice lacking COQ8A develop a slowly progressive cerebellar ataxia linked to Purkinje cell dysfunction and mild exercise intolerance, recapitulating ARCA2. Interspecies biochemical analyses show that COQ8A and yeast Coq8p specifically stabilize a CoQ biosynthesis complex through unorthodox PKL functions. Although COQ8 was predicted to be a protein kinase, we demonstrate that it lacks canonical protein kinase activity in trans. Instead, COQ8 has ATPase activity and interacts with lipid CoQ intermediates, functions that are likely conserved across all domains of life. Collectively, our results lend insight into the molecular activities of the ancient UbiB family and elucidate the biochemical underpinnings of a human disease.

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Type
research article
DOI
10.1016/j.molcel.2016.06.030
Web of Science ID

WOS:000381620300009

Author(s)
Stefely, Jonathan A.
Licitra, Floriana
Laredj, Leila
Reidenbach, Andrew G.
Kemmerer, Zachary A.
Grangeray, Anais
Jaeg-Ehret, Tiphaine
Minogue, Catherine E.
Ulbrich, Arne
Hutchins, Paul D.
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Date Issued

2016

Publisher

Cell Press

Published in
Molecular Cell
Volume

63

Issue

4

Start page

608

End page

620

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPDALPE  
Available on Infoscience
October 18, 2016
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/130328
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