ArticleThe EMBO journal2023
FBXL4 ubiquitin ligase deficiency promotes mitophagy by elevating NIX levels.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 54 citations in OpenAlex.
- The role of E3 ubiquitin ligases in selective types of macroautophagy.EMBO reports · 2026Review
- Regulation and roles of mammalian mitophagy.Nature reviews. Molecular cell biology · 2026Review
- Activation of AMPK as a therapeutic strategy for FBXL4-related mitochondrial DNA depletion syndrome.EMBO molecular medicine · 2026Article
- Sustained loss ofbioRxiv : the preprint server for biology · 2026Article
- Molecular diversity of mitochondrial autophagy receptors: context-dependent effects in human health and disease.Cell death discovery · 2026Review
- Mitophagy in Hepatic Ischemia-Reperfusion Injury: From Mitochondrial Dysfunction to Therapeutic Targeting.Biomolecules · 2026Review
- Two Routes for Removing Unhealthy Mitochondria: Degradation and Secretion.Circulation research · 2026Review
- Function and regulation of the mitochondrial stress response.Nature structural & molecular biology · 2026Review
- Recessive PPTC7 deficiency triggers excessive mitophagy to cause a severe inborn error of metabolism with hypomyelinating leukodystrophy.Research square · 2026Article
- CRISPR-based functional genomic screening in neurodegeneration: mechanistic insights into AD, PD, and ALS.Frontiers in aging neuroscience · 2026Review
- Mitophagy in the pathogenesis and management of disease.Cell research · 2026Review
- C9orf72-ALS mutation drives basal mitophagy impairments in iNeurons.Frontiers in cellular neuroscience · 2026Article
- Mitophagy and Cellular Homeostasis in Kidney Diseases: Mechanisms and Potential Therapeutics.International journal of biological sciences · 2026Review
- Mechanism of autophagy initiation by transmembrane selective autophagy receptors.The EMBO journal · 2025Review
- Stressful situations: Molecular insights on mitochondrial quality control pathways.The Journal of biological chemistry · 2025Review
- Targeting mitophagy in neurodegenerative diseases.Nature reviews. Drug discovery · 2025Review
- PPTC7 acts as an essential co-factor of the SCFCell death & disease · 2025Article
- Targeted proteomics addresses selectivity and complexity of protein degradation by autophagy.Autophagy · 2025Article
- Whole organism and tissue-specific analysis of pexophagy inOpen biology · 2025Article
- Longitudinal autophagy profiling of the mammalian brain reveals sustained mitophagy throughout healthy aging.The EMBO journal · 2024Article
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8 authors at 3 institutions in 2 countries.
Funding
Abstract
Selective autophagy of mitochondria, mitophagy, is linked to mitochondrial quality control and as such is critical to a healthy organism. We have used a CRISPR/Cas9 approach to screen human E3 ubiquitin ligases for influence on mitophagy under both basal cell culture conditions and upon acute mitochondrial depolarization. We identify two cullin-RING ligase substrate receptors, VHL and FBXL4, as the most profound negative regulators of basal mitophagy. We show that these converge, albeit via different mechanisms, on control of the mitophagy adaptors BNIP3 and BNIP3L/NIX. FBXL4 restricts NIX and BNIP3 levels via direct interaction and protein destabilization, while VHL acts through suppression of HIF1α-mediated transcription of BNIP3 and NIX. Depletion of NIX but not BNIP3 is sufficient to restore mitophagy levels. Our study contributes to an understanding of the aetiology of early-onset mitochondrial encephalomyopathy that is supported by analysis of a disease-associated mutation. We further show that the compound MLN4924, which globally interferes with cullin-RING ligase activity, is a strong inducer of mitophagy, thus providing a research tool in this context and a candidate therapeutic agent for conditions linked to mitochondrial dysfunction.
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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.