ArticleHuman molecular genetics2016
Drosophila clueless is involved in Parkin-dependent mitophagy by promoting VCP-mediated Marf degradation.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
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- The many faces of p97/Cdc48 in mitochondrial homeostasis.Essays in biochemistry · 2025Review
- RNAi-based screen for pigmentation inbioRxiv : the preprint server for biology · 2025Article
- Mitochondrial proteases and their roles in mitophagy in plants, animals, and yeast.Plant & cell physiology · 2025Review
- Loss of nuclear envelope bud formation leads to mitophagy initiation inAutophagy reports · 2025Article
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- CLUH maintains functional mitochondria and translation in motoneuronal axons and prevents peripheral neuropathy.Science advances · 2024Article
- Valosin-Containing Protein (VCP): A Review of Its Diverse Molecular Functions and Clinical Phenotypes.International journal of molecular sciences · 2024Review
- Mitochondrial Differentiation during Spermatogenesis: Lessons fromInternational journal of molecular sciences · 2024Review
- A conserved STRIPAK complex is required for autophagy in muscle tissue.Molecular biology of the cell · 2023Article
- The Drosophila gene encoding JIG protein (CG14850) is critical for CrebA nuclear trafficking during development.Nucleic acids research · 2023Article
- Stress-induced reversible cell-cycle arrest requires PRC2/PRC1-mediated control of mitophagy in Drosophila germline stem cells and human iPSCs.Stem cell reports · 2023Article
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- Disruption of the lipolysis pathway results in stem cell death through a sterile immunity-like pathway in adult Drosophila.Cell reports · 2022Article
- Mitochondria in neurodegeneration.Current opinion in physiology · 2022Article
- Clueless/CLUH regulates mitochondrial fission by promoting recruitment of Drp1 to mitochondria.Nature communications · 2022Article
- An exon junction complex-independent function of Barentsz in neuromuscular synapse growth.EMBO reports · 2022Article
- Article
- Autophagy in Drosophila and Zebrafish.Advances in experimental medicine and biology · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.