Evidence map›Paper›PMID 39416056›Full record

ArticlebioRxiv : the preprint server for biology2025

Cardiolipin deficiency disrupts electron transport chain to drive steatohepatitis.

Marisa J Brothwell, Guoshen Cao, J Alan Maschek, Annelise M Poss, Alek D Peterlin, Liping Wang, Talia B Baker, Justin L Shahtout, Piyarat Siripoksup, Quentinn J Pearce and 25 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

35 authors.

Marisa J BrothwellDiabetes & Metabolism Research Center; University of Utah; Salt Lake City, UT; USA.
Guoshen CaoDiabetes & Metabolism Research Center; University of Utah; Salt Lake City, UT; USA.
J Alan MaschekDiabetes & Metabolism Research Center; University of Utah; Salt Lake City, UT; USA.
Annelise M PossDiabetes & Metabolism Research Center; University of Utah; Salt Lake City, UT; USA.
Alek D PeterlinDiabetes & Metabolism Research Center; University of Utah; Salt Lake City, UT; USA.
Liping WangDiabetes & Metabolism Research Center; University of Utah; Salt Lake City, UT; USA.
Talia B BakerHuntsman Cancer Institute; University of Utah, Salt Lake City, UT; USA.
Justin L ShahtoutDiabetes & Metabolism Research Center; University of Utah; Salt Lake City, UT; USA.
Piyarat SiripoksupDiabetes & Metabolism Research Center; University of Utah; Salt Lake City, UT; USA.
Quentinn J PearceMetabolomics Core Research Facility; University of Utah; Salt Lake City, UT; USA.
Jordan M JohnsonDiabetes & Metabolism Research Center; University of Utah; Salt Lake City, UT; USA.
Fabian M FingerNovo Nordisk Foundation Center for Basic Metabolic Research; University of Copenhagen; Copenhagen; DK.
Alexandre ProlaLaboratory of Fundamental and Applied Bioenergetics; University of Grenoble Alpes, Inserm U1055; Grenoble; FR.
Sarah A PellizzariDepartment of Biochemistry; University of Utah; Salt Lake City, UT; USA.
Gillian L HaleHuntsman Cancer Institute; University of Utah, Salt Lake City, UT; USA.
Allison M ManuelMetabolomics Core Research Facility; University of Utah; Salt Lake City, UT; USA.
Shinya WatanabeDiabetes & Metabolism Research Center; University of Utah; Salt Lake City, UT; USA.
Edwin R MirandaDiabetes & Metabolism Research Center; University of Utah; Salt Lake City, UT; USA.
Kajsa E AffolterHuntsman Cancer Institute; University of Utah, Salt Lake City, UT; USA.
Trevor S TippettsDiabetes & Metabolism Research Center; University of Utah; Salt Lake City, UT; USA.
Linda S NikolovaElectron Microscopy Core Facility; University of Utah; Salt Lake City, UT; USA.
Ran Hee ChoiDiabetes & Metabolism Research Center; University of Utah; Salt Lake City, UT; USA.
Stephen T DeckerDiabetes & Metabolism Research Center; University of Utah; Salt Lake City, UT; USA.
Mallikarjun PatilDiabetes & Metabolism Research Center; University of Utah; Salt Lake City, UT; USA.
J Leon CatrowMetabolomics Core Research Facility; University of Utah; Salt Lake City, UT; USA.
William L HollandDiabetes & Metabolism Research Center; University of Utah; Salt Lake City, UT; USA.
Sara M NowinskiDepartment of Metabolism and Nutritional Programming; Van Andel Institute; Grand Rapids, MI; USA.
Daniel S LarkCollege of Health and Human Sciences; Colorado State University; Fort Collins, CO; USA.ORCID 0000-0001-8386-8478
Kelsey H Fisher-WellmanDepartment of Cancer Biology, Wake Forest University School of Medicine; Atrium Health Wake Forest Baptist Comprehensive Cancer Center; Winston-Salem, NC; USA.
Patrice N MimcheDepartments of Dermatology and Medicine; Division of Gastroenterology and Hepatology, Indiana University School of Medicine; Indianapolis, IN; USA.
Kimberley J EvasonHuntsman Cancer Institute; University of Utah, Salt Lake City, UT; USA.
James E CoxDiabetes & Metabolism Research Center; University of Utah; Salt Lake City, UT; USA.
Scott A SummersDiabetes & Metabolism Research Center; University of Utah; Salt Lake City, UT; USA.
Zach Gerhart-HinesNovo Nordisk Foundation Center for Basic Metabolic Research; University of Copenhagen; Copenhagen; DK.
Katsuhiko FunaiDiabetes & Metabolism Research Center; University of Utah; Salt Lake City, UT; USA.

Funding

UTAH REGIONAL CANCER CENTERP30CA042014 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Jared P Rutter · 1986 to 2026
$72.6M
WU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI Clay F. Semenkovich · 2013 to 2026
$27.1M
CTSA UM1 Program at University of UtahUM1TR004409 · NCATS · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI RACHEL HESS, Jennifer Juhl Majersik · 2023 to 2026
$21.9M
Proteomics CoreU54DK110858 · NIDDK · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Anna E Beaudin, JAMES Eric COX · 2016 to 2026
$8.6M
Interdisciplinary Training Program in MetabolismT32DK091317 · NIDDK · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI SCOTT A SUMMERS · 2011 to 2026
$4.8M
Ceramides as novel drivers of metabolic dysfunction and colorectal cancerU01CA272529 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Mary Christine Playdon, SCOTT A SUMMERS · 2022 to 2026
$4.7M
PE methylation in skeletal muscle energy efficiencyR01DK107397 · NIDDK · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI FUNAI, KATSUHIKO · 2017 to 2025
$3.8M
Liver-islet and intra-islet cross talk in alpha cell hyperplasia and beta cell regenerationR01DK112826 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI HOLLAND, WILLIAM L · 2017 to 2025
$3.4M
LOOH-induced muscle atrophy with ageR01AG074535 · NIA · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Micah J Drummond, Katsuhiko Funai · 2022 to 2026
$3.0M
Small molecule antagonists targeting EphB receptors for the treatment of nonalcoholic steatohepatitis (NASH)R01DK128819 · NIDDK · UNIVERSITY OF UTAH · PI MIMCHE, PATRICE · 2021 to 2025
$2.9M
The Role of Ceramides in the Intestinal Stem CellR01DK131609 · NIDDK · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI EDGAR, BRUCE ALEXANDER, SUMMERS, SCOTT A · 2021 to 2025
$2.5M
The Role of Ceramides in the Pancreatic Beta CellR01DK130296 · NIDDK · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI HOLLAND, WILLIAM L, SUMMERS, SCOTT A · 2022 to 2025
$2.2M
NCATS NIH HHS UM1 TR004409NCI NIH HHS P30 CA042014NCI NIH HHS R01 CA222570NCI NIH HHS U01 CA272529NHLBI NIH HHS R01 HL170575NIA NIH HHS R01 AG074535NIDDK NIH HHS F31 DK127603NIDDK NIH HHS F31 DK130555NIDDK NIH HHS P30 DK020579NIDDK NIH HHS R01 DK107397NIDDK NIH HHS R01 DK112826NIDDK NIH HHS R01 DK127979NIDDK NIH HHS R01 DK128819NIDDK NIH HHS R01 DK130296NIDDK NIH HHS R01 DK131609NIDDK NIH HHS R21 DK115991NIDDK NIH HHS T32 DK091317NIDDK NIH HHS U54 DK110858NIGMS NIH HHS R01 GM144613NIGMS NIH HHS R35 GM151245NIH HHS S10 OD016232NIH HHS S10 OD021505
6 · The paper itself

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive disorder marked by lipid accumulation, leading to metabolic dysfunction-associated steatohepatitis (MASH). A key feature of the transition to MASH involves oxidative stress resulting from defects in mitochondrial oxidative phosphorylation (OXPHOS). Here, we show that pathological alterations in the lipid composition of the inner mitochondrial membrane (IMM) directly instigate electron transfer inefficiency to promote oxidative stress. Specifically, mitochondrial cardiolipin (CL) was downregulated with MASLD/MASH in humans and in mice. Hepatocyte-specific CL synthase knockout (CLS-LKO) led to spontaneous and robust MASH with extensive steatotic and fibrotic phenotype. Loss of CL paradoxically increased mitochondrial respiratory capacity but also reduced the formation of I+III

Identifiers

PMID39416056
PMCPMC11482932

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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.