ArticleCell communication and signaling : CCS2025
TRAP1 inhibits KANSL3 acetylation to alleviate mitochondrial dysfunction by promoting mitophagy in cardiomyocytes under diabetic conditions.
Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 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
2 citing papers in PubMed.
- KAT8-mediated epigenetic modifications: Physiological functions, heterogeneity in disease, and advances in targeted development.iScience · 2026Review
- SIRT5-mediated HSDL2 desuccinylation promotes diabetic-associated cognitive dysfunction via disrupting mitochondrial TRAP1.Cell biology and toxicology · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
backgroundMitochondrial damage induced by glucolipotoxicity leads to cardiac dysfunction, known as cardiomyopathy. Timely clearance of damaged mitochondria is crucial for maintaining normal cardiac function. Mitophagy is the major mechanism underlying this process.
methodsAC16 cells were cultured under high glucose/palmitate (HG/PA) conditions to mimic diabetic cardiomyopathy (DCM). Tumor necrosis factor receptor-associated protein 1 (TRAP1) overexpression and KAT8 regulatory NSL complex subunit 3 (KANSL3) knockdown were achieved via lentiviral transduction. Cell viability was assessed using a Cell Counting Kit-8 (CCK8) assay. Mitochondrial morphology was observed using transmission electron microscopy and Mito-Tracker staining. Mitophagic flux was assessed using autophagy and mitophagy markers, mKeima fluorescence, and immunofluorescence colocalization. Mitochondrial function was assessed by measuring ATP content, the mitochondrial membrane potential (MMP), and mitochondrial oxidative stress. The animal studies used Sprague‒Dawley rats with streptozotocin (STZ)-induced diabetes and a high-fat diet to model DCM. Histological analyses, including H&E, Sirius Red, periodic acid–Schiff (PAS), and Masson staining, were conducted on heart tissue sections. Using immunoprecipitation (IP) and liquid chromatography–tandem mass spectrometry (LC‒MS/MS), we demonstrated that TRAP1 interacts with KANSL3 and that HG/PA conditions influence the acetylation status of KANSL3.
resultsOur study revealed that damaged mitochondria accumulation is a significant feature of cardiomyocytes under diabetic conditions, but no activated mitophagy was observed. Further joint analysis revealed that a mitophagy-related protein TRAP1 is significantly downregulated both in in vivo and in vitro models of DCM. Importantly, exogenous expression of TRAP1 restored mitophagy activity and alleviated mitochondrial dysfunction, highlighting the protective role of TRAP1 in cardiomyocytes under diabetic conditions. Mechanistically, TRAP1 was identified as a molecular chaperone that directly interacts with KANSL3, and this interaction was significantly decreased under diabetic conditions. We observed that the acetylation of KANSL3 is crucial for mitophagy dysfunction under diabetic conditions. TRAP1 inhibited KANSL3 acetylation to preserve mitophagy in cardiomyocytes under normal conditions, and downregulation of TRAP1 under diabetic conditions impaired mitophagy and mitochondrial dysfunction.
conclusionsCollectively, these results demonstrate that TRAP1 inhibits KANSL3 acetylation to mediate mitophagy and alleviate mitochondrial dysfunction in cardiomyocytes under diabetic conditions. Our findings provide a potential therapeutic target for DCM.
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.