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Citation
Zhang, Y., Wang, Z.H., Liu, Y., Chen, Y., Sun, N., Gucek, M., Zhang, F., Xu, H. (2019). PINK1 Inhibits Local Protein Synthesis to Limit Transmission of Deleterious Mitochondrial DNA Mutations.  Mol. Cell 73(6): 1127--1137.e5.
FlyBase ID
FBrf0241857
Publication Type
Research paper
Abstract

We have previously proposed that selective inheritance, the limited transmission of damaging mtDNA mutations from mother to offspring, is based on replication competition in Drosophila melanogaster. This model, which stems from our observation that wild-type mitochondria propagate much more vigorously in the fly ovary than mitochondria carrying fitness-impairing mutations, implies that germ cells recognize the fitness of individual mitochondria and selectively boost the propagation of healthy ones. Here, we demonstrate that the protein kinase PINK1 preferentially accumulates on mitochondria enriched for a deleterious mtDNA mutation. PINK1 phosphorylates Larp to inhibit protein synthesis on the mitochondrial outer membrane. Impaired local translation on defective mitochondria in turn limits the replication of their mtDNA and hence the transmission of deleterious mutations to the offspring. Our work confirms that selective inheritance occurs at the organelle level during Drosophila oogenesis and provides molecular entry points to test this model in other systems.

PubMed ID
PubMed Central ID
PMC7485087 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Mol. Cell
    Title
    Molecular Cell
    Publication Year
    1997-
    ISBN/ISSN
    1097-2765 1097-4164
    Data From Reference
    Alleles (21)
    Genes (6)
    Physical Interactions (1)
    Natural transposons (1)
    Insertions (17)
    Experimental Tools (3)
    Transgenic Constructs (15)