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Wang, Z.H., Clark, C., Geisbrecht, E.R. (2016). Drosophila clueless is involved in Parkin-dependent mitophagy by promoting VCP-mediated Marf degradation.  Hum. Mol. Genet. 25(10): 1946--1964.
FlyBase ID
FBrf0233735
Publication Type
Research paper
Abstract
PINK1/Parkin-mediated mitochondrial quality control (MQC) requires valosin-containing protein (VCP)-dependent Mitofusin/Marf degradation to prevent damaged organelles from fusing with the healthy mitochondrial pool, facilitating mitochondrial clearance by autophagy. Drosophila clueless (clu) was found to interact genetically with PINK1 and parkin to regulate mitochondrial clustering in germ cells. However, whether Clu acts in MQC has not been investigated. Here, we show that overexpression of Drosophila Clu complements PINK1, but not parkin, mutant muscles. Loss of clu leads to the recruitment of Parkin, VCP/p97, p62/Ref(2)P and Atg8a to depolarized swollen mitochondria. However, clearance of damaged mitochondria is impeded. This paradox is resolved by the findings that excessive mitochondrial fission or inhibition of fusion alleviates mitochondrial defects and impaired mitophagy caused by clu depletion. Furthermore, Clu is upstream of and binds to VCP in vivo and promotes VCP-dependent Marf degradation in vitro Marf accumulates in whole muscle lysates of clu-deficient flies and is destabilized upon Clu overexpression. Thus, Clu is essential for mitochondrial homeostasis and functions in concert with Parkin and VCP for Marf degradation to promote damaged mitochondrial clearance.
PubMed ID
PubMed Central ID
PMC5062585 (PMC) (EuropePMC)
Related Publication(s)
Erratum

Corrigendum to: Drosophila clueless is involved in Parkin-dependent mitophagy by promoting VCP-mediated Marf degradation.
Wang et al., 2020, Hum. Mol. Genet. 29(12): 2107 [FBrf0246302]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Hum. Mol. Genet.
    Title
    Human Molecular Genetics
    Publication Year
    1992-
    ISBN/ISSN
    0964-6906
    Data From Reference