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Citation
Gehrke, S., Wu, Z., Klinkenberg, M., Sun, Y., Auburger, G., Guo, S., Lu, B. (2015). PINK1 and Parkin control localized translation of respiratory chain component mRNAs on mitochondria outer membrane.  Cell Metab. 21(1): 95--108.
FlyBase ID
FBrf0229600
Publication Type
Research paper
Abstract

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.

Graphical Abstract
Obtained with permission from Cell Press.
PubMed ID
PubMed Central ID
PMC4455944 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cell Metab.
    Title
    Cell Metabolism
    Publication Year
    2005-
    ISBN/ISSN
    1550-4131
    Data From Reference
    Alleles (43)
    Genes (31)
    Human Disease Models (2)
    Physical Interactions (5)
    Natural transposons (1)
    Experimental Tools (1)
    Transgenic Constructs (38)