Evidence map›Paper›PMID 39760651›Full record

ArticleThe journal of trauma and acute care surgery2025

Burn-induced mitochondrial dysfunction in hepatocytes: The role of methylation-controlled J protein silencing.

Akshay Pratap, Kenneth Meza Monge, Andrea C Qualman, Elizabeth J Kovacs, Juan-Pablo Idrovo

Abstract read
In one paragraph

Article in The journal of trauma and acute care surgery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Akshay PratapFrom the Division of Gastrointestinal, Trauma, and Endocrine Surgery, Department of Surgery (A.P., K.M.M., A.C.Q., E.J.K., J.-P.I.), Division of Burn Research (E.J.K.), and Division of Alcohol Research (E.J.K.), Department of Immunology and Microbiology, University of Colorado, Aurora, Colorado.
Kenneth Meza Monge
Andrea C Qualman
Elizabeth J Kovacs
Juan-Pablo Idrovo

Funding

Alcohol and Burn Trauma: Multi-organ Inflammatory ResponsesR35GM131831 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI ELIZABETH J. KOVACS · 2019 to 2026
$3.5M
Aging, Burn Trauma, and Liver DamageR01GM153949 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI Juan Pablo Idrovo · 2024 to 2026
$1.0M
Hepatic Response in Advance Age after Burn InjuryK08GM134185 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI IDROVO, JUAN PABLO · 2019 to 2023
$945k
NIGMS NIH HHS K08 GM134185NIGMS NIH HHS R01 GM153949NIGMS NIH HHS R35 GM131831
6 · The paper itself

Abstract

backgroundBurn injuries trigger a systemic hyperinflammatory response, leading to multiple organ dysfunction, including significant hepatic damage. The liver plays a crucial role in regulating immune responses and metabolism after burn injuries, making it critical to develop strategies to mitigate hepatic impairment. This study investigates the role of methylation-controlled J protein (MCJ), an inner mitochondrial protein that represses complex I in burn-induced oxidative stress and mitochondrial dysfunction, using an in vitro Alpha Mouse Liver 12 cell model.

methodsAlpha Mouse Liver 12 cells were treated with serum from burn-injured mice (SBIM) to simulate burn injury in vitro. Methylation-controlled J protein was silenced using shRNA. Cell viability, apoptosis markers, reactive oxygen species levels, antioxidant response elements, electron transport chain components, and mitochondrial respiration were assessed using various techniques, including Cell Counting Kit-8 assay, Western blotting, MitoSOX Red staining, and Seahorse XF analysis.

resultsSerum from burn-injured mice treatment (10%) for 8 hours reduced Alpha Mouse Liver 12 cell viability to 50% of control levels and increased MCJ expression fivefold. It also significantly upregulated apoptosis markers: cleaved caspase-3 (4-fold), Bax (3.8-fold), and cytosolic cytochrome c (3.5-fold). Methylation-controlled J protein silencing improved cell viability to 85% of control levels and reduced apoptosis markers by 75% to 78%. Serum from burn-injured mice increased reactive oxygen species levels by 3-fold, while MCJ silencing reduced this by 2.5-fold. Antioxidant proteins (NRF2, HO-1, NQO-1, GCLC, catalase) were suppressed by SBIM but upregulated 3.2- to 3.8-fold with MCJ silencing. Serum from burn-injured mice reduced electron transport chain components (NDUFS1, SDHB, MTCO2) by 45% to 65%, which MCJ silencing restored 2.5- to 3-fold. Mitochondrial respiration improved significantly with MCJ silencing: basal respiration (+26%), maximal respiration (+66%), adenosine triphosphate production (+25%), and spare respiratory capacity (+63%).

conclusionMethylation-controlled J protein plays a critical role in burn-induced hepatocyte damage. Its silencing alleviates SBIM-induced cytotoxicity, oxidative stress, and mitochondrial dysfunction. These findings highlight MCJ as a potential therapeutic target for preserving liver function in burn patients, warranting further in vivo studies to explore its clinical potential.

Indexed as

BurnsHepatocytesMitochondria, LiverMitochondrial ProteinsAnimalsApoptosisCell SurvivalDisease Models, AnimalGene SilencingMaleMiceMice, Inbred C57BLOxidative StressReactive Oxygen SpeciesMitochondrial ProteinsReactive Oxygen Species

Identifiers

PMID39760651
PMCPMC11838791

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Registered trials

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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 Socratic graph.