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PINK1 and Parkin control localized translation of respiratory chain component mRNAs on mitochondria outer membrane.

Cell Metab.2015 Jan 06;21(1):95-108
Stephan Gehrke 1 , Zhihao Wu 1 , Michael Klinkenberg 2 , Yaping Sun 3 , Georg Auburger 2 , Su Guo 4 , Bingwei Lu 5
Stephan Gehrke 1 , Zhihao Wu 1 , Michael Klinkenberg 2 , Yaping Sun 3 , Georg Auburger 2 , Su Guo 4 , Bingwei Lu 5
+ et al

[No authors listed]

Author information
  • 1 Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 2 Experimental Neurology, Goethe University Medical School, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.
  • 3 Department of Bioengineering and Therapeutic Sciences, Programs in Biological Sciences and Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA.
  • 4 Department of Bioengineering and Therapeutic Sciences, Programs in Biological Sciences and Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: su.guo@ucsf.edu.
  • 5 Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: bingwei@stanford.edu.

摘要

Mitochondria play essential roles in many aspects of biology, and their dysfunction has been linked to diverse diseases. Central to mitochondrial function is oxidative phosphorylation (OXPHOS), accomplished by respiratory chain complexes (RCCs) encoded by nuclear and mitochondrial genomes. How RCC biogenesis is regulated in metazoans is poorly understood. Here we show that Parkinson's disease (PD)-associated genes PINK1 and Parkin direct localized translation of certain nuclear-encoded RCC (nRCC) mRNAs. Translationally repressed nRCC mRNAs are localized in a PINK1/Tom20-dependent manner to mitochondrial outer membrane, where they are derepressed and activated by PINK1/Parkin through displacement of translation repressors, including Pumilio and Glorund/hnRNP-F, a Parkin substrate, and enhanced binding of activators such as eIF4G. Inhibiting the translation repressors rescued nRCC mRNA translation and neuromuscular-degeneration phenotypes of PINK1 mutant, whereas inhibiting eIF4G had opposite effects. Our results reveal previously unknown functions of PINK1/Parkin in RNA metabolism and suggest new approaches to mitochondrial restoration and disease intervention.

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