Evidence map›Paper›PMID 42684124›Full record

ArticleeLife2026

Cardiolipin deficiency disrupts electron transport chain and drives 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

Abstract read
In one paragraph

Article in eLife, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Mitochondrial Calcium Signaling in Hepatocyte Health and Disease.Cold Spring Harbor perspectives in biology · 2026
    Review
  3. Review
  4. Article
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

35 authors.

Marisa J BrothwellCenter of Metabolic Health, University of Utah, Salt Lake City, United States.
Guoshen CaoCenter of Metabolic Health, University of Utah, Salt Lake City, United States.
J Alan MaschekCenter of Metabolic Health, University of Utah, Salt Lake City, United States.
Annelise M PossCenter of Metabolic Health, University of Utah, Salt Lake City, United States.
Alek D PeterlinCenter of Metabolic Health, University of Utah, Salt Lake City, United States.ORCID https://orcid.org/0000-0002-2837-7446
Liping WangCenter of Metabolic Health, University of Utah, Salt Lake City, United States.ORCID https://orcid.org/0000-0003-3537-0952
Talia B BakerHuntsman Cancer Institute, University of Utah, Salt Lake City, United States.
Justin L ShahtoutCenter of Metabolic Health, University of Utah, Salt Lake City, United States.
Piyarat SiripoksupCenter of Metabolic Health, University of Utah, Salt Lake City, United States.
Quentinn J PearceMetabolomics Core Research Facility, University of Utah, Salt Lake City, United States.
Jordan M JohnsonCenter of Metabolic Health, University of Utah, Salt Lake City, United States.
Fabian M FingerNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Alexandre ProlaLaboratory of Fundamental and Applied Bioenergetics, University of Grenoble Alpes, Grenoble, France.
Sarah A PellizzariDepartment of Biochemistry, University of Utah, Salt Lake City, United States.
Gillian L HaleHuntsman Cancer Institute, University of Utah, Salt Lake City, United States.
Allison M ManuelMetabolomics Core Research Facility, University of Utah, Salt Lake City, United States.
Shinya WatanabeCenter of Metabolic Health, University of Utah, Salt Lake City, United States.
Edwin R MirandaCenter of Metabolic Health, University of Utah, Salt Lake City, United States.ORCID https://orcid.org/0000-0003-2370-4118
Kajsa E AffolterHuntsman Cancer Institute, University of Utah, Salt Lake City, United States.
Trevor S TippettsCenter of Metabolic Health, University of Utah, Salt Lake City, United States.
Linda S NikolovaElectron Microscopy Core Facility, University of Utah, Salt Lake City, United States.
Ran Hee ChoiCenter of Metabolic Health, University of Utah, Salt Lake City, United States.
Stephen T DeckerCenter of Metabolic Health, University of Utah, Salt Lake City, United States.
Mallikarjun PatilCenter of Metabolic Health, University of Utah, Salt Lake City, United States.
J Leon CatrowMetabolomics Core Research Facility, University of Utah, Salt Lake City, United States.
William L HollandCenter of Metabolic Health, University of Utah, Salt Lake City, United States.
Sara M NowinskiDepartment of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, United States.
Daniel S LarkCollege of Health and Human Sciences, Colorado State University, Fort Collins, United States.ORCID https://orcid.org/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, United States.
Patrice N MimcheDepartments of Dermatology and Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, United States.
Kimberley EvasonHuntsman Cancer Institute, University of Utah, Salt Lake City, United States.ORCID https://orcid.org/0000-0002-0471-2473
James E CoxCenter of Metabolic Health, University of Utah, Salt Lake City, United States.
Scott A SummersCenter of Metabolic Health, University of Utah, Salt Lake City, United States.ORCID https://orcid.org/0000-0002-4919-0592
Zach Gerhart-HinesNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.ORCID https://orcid.org/0000-0003-2981-4991
Katsuhiko FunaiCenter of Metabolic Health, University of Utah, Salt Lake City, United States.ORCID https://orcid.org/0000-0003-3802-4756

Funding

PE methylation in skeletal muscle energy efficiencyR01DK107397 · NIDDK · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI FUNAI, KATSUHIKO · 2017 to 2025
$3.8M
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
Lands cycle and skeletal muscle insulin actionR01DK127979 · NIDDK · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI FUNAI, KATSUHIKO · 2022 to 2025
$1.9M
PE In Modulation of Energy Flux Through OxphosR01GM144613 · NIGMS · UNIVERSITY OF UTAH · PI FUNAI, KATSUHIKO · 2021 to 2024
$1.6M
NIA NIH HHS AG074535NIA NIH HHS R01 AG074535NIDDK NIH HHS DK107397NIDDK NIH HHS DK127979NIDDK NIH HHS R01 DK107397NIDDK NIH HHS R01 DK127979NIGMS NIH HHS GM144613NIGMS NIH HHS R01 GM144613
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 promoted electron leak primarily at sites III

Indexed as

CardiolipinsFatty LiverAnimalsElectron TransportHepatocytesHumansMembrane ProteinsMiceMice, KnockoutMitochondriaOxidative PhosphorylationOxidative StressTransferases (Other Substituted Phosphate Groups)Cardiolipinscardiolipin synthetaseMembrane ProteinsTransferases (Other Substituted Phosphate Groups)cardiolipincell biologyhumanlivermitochondriamouse

Identifiers

PMID42684124
PMCPMC13537762

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.