ArticleCellular and molecular gastroenterology and hepatology2024
Hepatocyte Deubiquitinating Enzyme OTUD5 Deficiency is a Key Aggravator for Metabolic Dysfunction-Associated Steatohepatitis by Disturbing Mitochondrial Homeostasis.
Article in Cellular and molecular gastroenterology and hepatology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- USP2 promotes metabolic dysfunction-associated steatotic liver disease progression via stabilization of PPARγ.Cell death and differentiation · 2026Article
- Deubiquitinases in liver diseases: from mechanisms to targeted therapy.Science China. Life sciences · 2026Review
- OTU deubiquitinases in disease: roles and targeting.Trends in molecular medicine · 2026Review
- Ubiquitination modifications as central regulators of metabolic dysfunction in type 2 diabetes mellitus.Frontiers in endocrinology · 2026Review
- Ubiquitination and ubiquitin-like modifications in metabolic dysfunction-associated steatotic liver disease: mechanisms and implications.BMB reports · 2025Review
- USP25 directly interacts with and deubiquitinates PPARα to increase PPARα stability in hepatocytes and attenuate high-fat diet-induced MASLD in mice.Cell death and differentiation · 2025Article
- Osteocyte-derived extracellular vesicles mediate the bone-to-cartilage crosstalk and promote osteoarthritis progression.Nature communications · 2025Article
- OTUD5 promotes the inflammatory immune response by enhancing MyD88 oligomerization and Myddosome formation.Cell death and differentiation · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsMetabolic dysfunction-associated steatohepatitis (MASH) is a common chronic liver disease worldwide. No effective pharmacologic therapies for MASH have been developed; to develop such promising drugs, the underlying mechanisms regulating MASH need to be elucidated. Here, we aimed to determine the role of ovarian tumor domain-containing protein 5 (OTUD5) in MASH progression and identify a specific mechanism.
methodsThe expression levels of OTUD subfamily under palmitic acid/oleic acid (PAOA) stimulation were screened. OTUD5 expression was assessed in human liver tissues without steatosis, those with simple steatosis, and those with MASH. MASH models were developed in hepatocyte-specific Otud5-knockout mice that were fed high-fat high-cholesterol and high-fat high-cholesterol plus high-fructose/sucrose diet for 16 weeks.
resultsThe expression of OTUD5 was down-regulated in fatty liver and was negatively related to the progression of MASH. Lipid accumulation and inflammation were exacerbated by Otud5 knockdown but attenuated by Otud5 overexpression under PAOA treatment. Hepatocyte-specific Otud5 deletion markedly exacerbated steatosis, inflammation, and fibrosis in the livers of 2 MASH mouse models. We identified voltage-dependent anion channel 2 (VDAC2) as an OTUD5-interacting partner; OTUD5 cleaved the K48-linked polyubiquitin chains from VDAC2, and it inhibited subsequent proteasomal degradation. The anabolic effects of OTUD5 knockdown on PAOA-induced lipid accumulation were effectively reversed by VDAC2 overexpression in primary hepatocytes. Metabolomic results revealed that VDAC2 is required for OTUD5-mediated protection against hepatic steatosis by maintaining mitochondrial function.
conclusionsOTUD5 may ameliorate MASH progression via VDAC2-maintained mitochondrial homeostasis. Targeting OTUD5 may be a viable MASH-treatment strategy.
Indexed as
Identifiers
What OpenQuestion holds
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.