ArticleScience (New York, N.Y.)2025
Retrograde mitochondrial signaling governs the identity and maturity of metabolic tissues.
Abstract read
In one paragraph
Article in Science (New York, N.Y.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
–field-weighted citation impact
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
47 citing papers in PubMed.
- Modulating Ubiquinone Biosynthesis Rescues Mitochondrial Dysfunction by Genetic Interaction in a Phosphatidylethanolamine (PE)-Deficient Disease Model.Antioxidants (Basel, Switzerland) · 2026Article
- Metabolites with a message: impacts on epigenetics and implications for epimetabopathies.EMBO reports · 2026Review
- GPR180 deficiency impairs mitochondrial function and insulin secretion in pancreatic β-cells.Molecular metabolism · 2026Article
- The central role of the β-cell in diabetes: from monogenic forms to type 1, type 2, and gestational diabetes.Reviews in endocrine & metabolic disorders · 2026Review
- Mitochondrial structural and functional aberrations in diabetic bladder dysfunction: underlying mechanisms and therapeutic landscapes.Acta diabetologica · 2026Review
- An epigenetic switch in β-cells links mitochondrial stress to inflammatory fate via HMGB1 acetylation.Cell death and differentiation · 2026Article
- Metabolic reprogramming drives pancreatic β cell neogenesis from α cells.Nature chemical biology · 2026Article
- Review
- Molecular damage associated with ageing drives inflammation in cardiovascular disease.Nature reviews. Cardiology · 2026Review
- Mitochondrial Quality Control in Age-Related Diseases: From Molecular Architecture to Precision Therapeutics.Antioxidants (Basel, Switzerland) · 2026Review
- Food Coloring Additives and Incidence of Type 2 Diabetes in the NutriNet-Santé Prospective Cohort.Diabetes care · 2026Article
- Cardiolipin preserves TNature metabolism · 2026Article
- Supervised machine learning identifies impaired mitochondrial quality control in β-cells with development of type 2 diabetes.NPJ systems biology and applications · 2026Article
- Zinc accumulation-induced integrated stress response triggers β-cell identity loss.Cell research · 2026Article
- Mitochondrial Homeostasis in Pancreatic β Cell Function: Mechanisms and Therapeutic Targets for Diabetes.Journal of diabetes · 2026Review
- Dynamic collaboration between mitochondria and organelles: mechanisms, functions, and disease implications.Apoptosis : an international journal on programmed cell death · 2026Review
- Resveratrol Attenuates Liver Inflammation in Non-Alcoholic Fatty Liver Disease by Activating PINK1-Mediated Mitophagy.Animals : an open access journal from MDPI · 2026Article
- Maternal obesity disrupts epigenetic reprogramming via peroxisomal-dependent phospholipid-methyl uncoupling during zygotic genome activation.Nature communications · 2026Article
- PGM1 deficiency is linked to sarcomeric and mitochondrial dysfunction in patient-derived iPSC-cardiomyocytes.Journal of translational medicine · 2026Article
- c-Myc/GRPEL1 maintains fatty acid synthesis via FASN to support PDAC cell proliferation.Cell death & disease · 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
30 authors.
Emily M Walker *Division of Metabolism, Endocrinology & Diabetes and Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0001-8394-1567
Gemma L Pearson *Division of Metabolism, Endocrinology & Diabetes and Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0003-4253-1830
Nathan LawlorThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.ORCID 0000-0003-3263-6057
Ava M StendahlDivision of Metabolism, Endocrinology & Diabetes and Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Anne LietzkeDivision of Metabolism, Endocrinology & Diabetes and Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0003-1334-1181
Vaibhav SidaralaDivision of Metabolism, Endocrinology & Diabetes and Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-8010-3418
Jie ZhuDivision of Metabolism, Endocrinology & Diabetes and Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Tracy StromerDivision of Metabolism, Endocrinology & Diabetes and Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Emma C ReckDivision of Metabolism, Endocrinology & Diabetes and Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Jin LiDivision of Metabolism, Endocrinology & Diabetes and Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-5743-696X
Elena Levi-D'AnconaDivision of Metabolism, Endocrinology & Diabetes and Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-4728-1976
Mabelle B PasmooijDivision of Metabolism, Endocrinology & Diabetes and Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.ORCID 0009-0004-7750-313X
Dre L HubersDivision of Metabolism, Endocrinology & Diabetes and Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.ORCID 0009-0001-4276-3714
Aaron RenbergDivision of Metabolism, Endocrinology & Diabetes and Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-8782-9342
Kawthar MohamedDivision of Metabolism, Endocrinology & Diabetes and Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Vishal S ParekhDepartment of Pharmacology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0001-6349-4077
Irina X ZhangDepartment of Pharmacology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0003-0078-1225
Benjamin ThompsonDepartment of Pharmacology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0003-2035-1337
Deqiang ZhangDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Sarah A WareVascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0002-2387-1613
Leena HaatajaDivision of Metabolism, Endocrinology & Diabetes and Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0003-3701-4679
Nathan QiDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0003-1919-9171
Stephen C J ParkerDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0001-8122-0117
Peter ArvanDivision of Metabolism, Endocrinology & Diabetes and Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-4007-8799
Lei YinDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Brett A KaufmanVascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0003-4767-4937
Leslie S SatinDepartment of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
Lori SusselBarbara Davis Center for Diabetes, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.ORCID 0000-0003-4672-7304
Michael L StitzelThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.ORCID 0000-0001-5630-559X
Scott A SoleimanpourDivision of Metabolism, Endocrinology & Diabetes and Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0001-6777-4498
Funding
Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Scott Soleimanpour · 2013 to 2026
$24.3MIntegrated Islet Distribution Program (U24) - 2021U24DK098085 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI Carmella Evans-Molina, Joyce Carol Niland · 2021 to 2026
$17.8MUniversity of Colorado Anschutz Medical Campus DRCP30DK116073 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI Maki Nakayama · 2020 to 2026
$10.8MProinsulin Trafficking for Insulin BiosynthesisR01DK048280 · NIDDK · YESHIVA UNIVERSITY · PI ARVAN, PETER · 1994 to 2024
$10.5MMETABOLICALLY-COUPLED ION CHANNEL INTERACTIONS IN ISLETSR01DK046409 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI SATIN, LESLIE S. · 1994 to 2023
$9.1MRegulation of Pancreatic Islet Cell FateR01DK082590 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI LORI SUSSEL · 2009 to 2026
$7.3MCellular and Molecular Biology at MichiganT32GM145470 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI John Chadwick Brenner · 2022 to 2026
$4.1MMetabolic Phenotyping in Live Models of Obesity and DiabetesU2CDK135066 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Nathan R. Qi · 2023 to 2026
$3.5MType 2 diabetes risk variant effects on mitochondrial (patho)physiologyR01DK136671 · NIDDK · JACKSON LABORATORY · PI Scott Soleimanpour, Michael Lee Stitzel · 2023 to 2026
$3.0MFunctional interaction of transcriptional regulators in endocrine lineage specificationR01DK135032 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Maureen A Gannon, DORIS A STOFFERS · 2023 to 2026
$2.8MA Stress-Induced Vicious Cycle In The Development of T1DU01DK127747 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ARVAN, PETER, SATIN, LESLIE S. · 2020 to 2023
$2.8MControl of insulin secretion by mitochondrial fusionR01DK135268 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Brett A Kaufman, Scott Soleimanpour · 2023 to 2026
$2.4MBLRD VA I01 BX004444NIDDK NIH HHS K01 DK133533NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P30 DK116073NIDDK NIH HHS R01 DK046409NIDDK NIH HHS R01 DK048280NIDDK NIH HHS R01 DK082590NIDDK NIH HHS R01 DK108921NIDDK NIH HHS R01 DK127270NIDDK NIH HHS R01 DK135032NIDDK NIH HHS R01 DK135268NIDDK NIH HHS R01 DK136671NIDDK NIH HHS R01 DK142799NIDDK NIH HHS U01 DK127747NIDDK NIH HHS U24 DK098085NIDDK NIH HHS U2C DK135066NIGMS NIH HHS T32 GM145470
Abstract
Mitochondrial damage is a hallmark of metabolic diseases, including diabetes, yet the consequences of compromised mitochondria in metabolic tissues are often unclear. In this work, we report that dysfunctional mitochondrial quality control engages a retrograde (mitonuclear) signaling program that impairs cellular identity and maturity in β cells, hepatocytes, and brown adipocytes. Targeted deficiency throughout the mitochondrial quality control pathway, including genome integrity, dynamics, or turnover, impaired the oxidative phosphorylation machinery, activating the mitochondrial integrated stress response, eliciting chromatin remodeling, and promoting cellular immaturity rather than apoptosis to yield metabolic dysfunction. Pharmacologic blockade of the integrated stress response in vivo restored β cell identity after the loss of mitochondrial quality control. Targeting mitochondrial retrograde signaling may therefore be promising in the treatment or prevention of metabolic disorders.
Indexed as
Adipocytes, BrownHepatocytesInsulin-Secreting CellsMitochondriaSignal TransductionAnimalsChromatin Assembly and DisassemblyMiceMitochondria, LiverOxidative PhosphorylationOxidative Stress
Identifiers
What Socratic holds
Textmetadata
LicenceTDM
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.