ArticleRedox biology2020
A new target for an old DUB: UCH-L1 regulates mitofusin-2 levels, altering mitochondrial morphology, function and calcium uptake.
Article in Redox biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- The Emerging Roles of E3 Ligases and DUBs in Neurodegenerative Diseases.Molecular neurobiology · 2023Pooled it
- Rodent models and accompanying in vitro strategies for studying the etiology and therapy of Parkinson's disease.Journal of Parkinson's disease · 2026Review
- USP16 regulates mitochondrial function by deubiquitinating TOM40, a core component of the translocase in the mitochondrial outer membrane.Cell death & disease · 2026Article
- Ketogenic diet regulates Uch-L1(C) to improve cerebral energy metabolism and cognitive function in Alzheimer's disease mice.European journal of histochemistry : EJH · 2026Article
- Milk fat globule-EGF factor 8/ATP-binding cassette subfamily E member 1 axis maintains mitophagy flux homeostasis to suppress ferroptosis in acute pancreatitis.Clinical and translational medicine · 2026Article
- Preclinical evaluation of waste-derived pomegranate extract (PWE) as a potential preventing and therapeutic agent for benign prostatic hyperplasia.Frontiers in molecular biosciences · 2026Article
- Protein farnesylation: from molecular mechanisms to therapeutic targeting in cancer, aging, and beyond.Frontiers in pharmacology · 2026Review
- Engineered thoracic spinal cord organoids for transplantation after spinal cord injury.Nature biomedical engineering · 2025Article
- Untargeted Metabolomics Uncovers Food Safety Risks: Polystyrene Nanoplastics Induce Metabolic Disorders in Chicken Liver.Foods (Basel, Switzerland) · 2025Article
- Role of mitochondria in physiological activities, diseases, and therapy.Molecular biomedicine · 2025Review
- Redox-driven regulation of UCHL3/Yuh1 influences mitochondrial health via the NEDD8/Rub1 pathway.Redox biology · 2025Article
- Redox regulation, protein S-nitrosylation, and synapse loss in Alzheimer's and related dementias.Neuron · 2024Review
- Ubiquitin Carboxyl-Terminal Hydrolase L1 and Its Role in Parkinson's Disease.International journal of molecular sciences · 2024Review
- UCHL1 alleviates apoptosis in chondrocytes via upregulation of HIF‑1α‑mediated mitophagy.International journal of molecular medicine · 2023Article
- Animal models of Parkinson's disease: bridging the gap between disease hallmarks and research questions.Translational neurodegeneration · 2023Review
- Review
- Osteopontin depletion in macrophages perturbs proteostasisFrontiers in immunology · 2023Article
- Role of the deubiquitinating enzyme UCH-L1 in mitochondrial function.Frontiers in cellular neuroscience · 2023Article
- Mitochondria, mitophagy, and the role of deubiquitinases as novel therapeutic targets in liver pathology.Journal of cellular biochemistry · 2022Review
- Mitofusins: from mitochondria to fertility.Cellular and molecular life sciences : CMLS · 2022Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 4 countries.
Funding
Abstract
UCH-L1 is a deubiquitinating enzyme (DUB), highly abundant in neurons, with a sub-cellular localization dependent on its farnesylation state. Despite UCH-L1's association with familial Parkinson's Disease (PD), the effects on mitochondrial bioenergetics and quality control remain unexplored. Here we investigated the role of UCHL-1 in mitochondrial dynamics and bioenergetics. We demonstrate that knock-down (KD) of UCH-L1 in different cell lines reduces the levels of the mitochondrial fusion protein Mitofusin-2, but not Mitofusin-1, resulting in mitochondrial enlargement and disruption of the tubular network. This was associated with lower tethering between mitochondria and the endoplasmic reticulum, consequently altering mitochondrial calcium uptake. Respiratory function was also altered, as UCH-L1 KD cells displayed higher proton leak and maximum respiratory capacity. Conversely, overexpression of UCH-L1 increased Mfn2 levels, an effect dramatically enhanced by the mutation of the farnesylation site (C220S), which drives UCH-L1 binding to membranes. These data indicate that the soluble cytosolic form of UCH-L1 regulates Mitofusin-2 levels and mitochondrial function. These effects are biologically conserved, since knock-down of the corresponding UCH-L1 ortholog in D. melanogaster reduces levels of the mitofusin ortholog Marf and also increases mitochondrial respiratory capacity. We thus show that Mfn-2 levels are directly affected by UCH-L1, demonstrating that the mitochondrial roles of DUBs go beyond controlling mitophagy rates.
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Registered trials
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.