Inhibition of mammalian mtDNA transcription acts paradoxically to reverse diet-induced hepatosteatosis and obesity.


Journal

Nature metabolism
ISSN: 2522-5812
Titre abrégé: Nat Metab
Pays: Germany
ID NLM: 101736592

Informations de publication

Date de publication:
30 Apr 2024
Historique:
received: 03 11 2022
accepted: 28 03 2024
medline: 1 5 2024
pubmed: 1 5 2024
entrez: 30 4 2024
Statut: aheadofprint

Résumé

The oxidative phosphorylation system

Identifiants

pubmed: 38689023
doi: 10.1038/s42255-024-01038-3
pii: 10.1038/s42255-024-01038-3
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Vetenskapsrådet (Swedish Research Council)
ID : 2015-00418
Organisme : Swedish Cancer Foundation
ID : CAN2018/602
Organisme : Novo Nordisk Fonden (Novo Nordisk Foundation)
ID : NNF20OC006316
Organisme : European Molecular Biology Organization (EMBO)
ID : ALTF570-2019
Organisme : European Molecular Biology Organization (EMBO)
ID : ALTF399-2021

Informations de copyright

© 2024. The Author(s).

Références

Fernandez‐Vizarra, E. & Zeviani, M. Mitochondrial disorders of the OXPHOS system. FEBS Lett. 595, 1062–1106 (2021).
doi: 10.1002/1873-3468.13995 pubmed: 33159691
Spinelli, J. B. & Haigis, M. C. The multifaceted contributions of mitochondria to cellular metabolism. Nat. Cell Biol. 20, 745–754 (2018).
doi: 10.1038/s41556-018-0124-1 pubmed: 29950572 pmcid: 6541229
Martínez-Reyes, I. & Chandel, N. S. Mitochondrial TCA cycle metabolites control physiology and disease. Nat. Commun. 11, 102 (2020).
doi: 10.1038/s41467-019-13668-3 pubmed: 31900386 pmcid: 6941980
Heiden, M. G. V., Cantley, L. C. & Thompson, C. B. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324, 1029–1033 (2009).
doi: 10.1126/science.1160809
Vasan, K., Werner, M. & Chandel, N. S. Mitochondrial metabolism as a target for cancer therapy. Cell Metab. https://doi.org/10.1016/j.cmet.2020.06.019 (2020).
doi: 10.1016/j.cmet.2020.06.019 pubmed: 32668195 pmcid: 7483781
Bonekamp, N. A. et al. Small-molecule inhibitors of human mitochondrial DNA transcription. Nature 588, 712–716 (2020).
doi: 10.1038/s41586-020-03048-z pubmed: 33328633
Grundlingh, J., Dargan, P. I., El-Zanfaly, M. & Wood, D. M. 2,4-Dinitrophenol (DNP): a weight loss agent with significant acute toxicity and risk of death. J. Med. Toxicol. 7, 205 (2011).
doi: 10.1007/s13181-011-0162-6 pubmed: 21739343 pmcid: 3550200
Tainter, M. L., Cutting, W. C. & Stockton, A. B. Use of dinitrophenol in nutritional disorders: a critical survey of clinical results. Am. J. Public Health Nations Health 24, 1045–1053 (1934).
doi: 10.2105/AJPH.24.10.1045 pubmed: 18014064 pmcid: 1558869
Cutting, W. C., Mehrtens, H. G. & Tainter, M. L. Actions and uses of dinitrophenol: promising metabolic applications. J. Am. Med. Assoc. 101, 193–195 (1933).
doi: 10.1001/jama.1933.02740280013006
Pernicova, I. & Korbonits, M. Metformin—mode of action and clinical implications for diabetes and cancer. Nat. Rev. Endocrinol. 10, 143–156 (2014).
doi: 10.1038/nrendo.2013.256 pubmed: 24393785
Feng, J. et al. Mitochondria as an important target of metformin: the mechanism of action, toxic and side effects, and new therapeutic applications. Pharmacol. Res. 177, 106114 (2022).
doi: 10.1016/j.phrs.2022.106114 pubmed: 35124206
Bridges, H. R., Jones, A. J. Y., Pollak, M. N. & Hirst, J. Effects of metformin and other biguanides on oxidative phosphorylation in mitochondria. Biochem. J. 462, 475–487 (2014).
doi: 10.1042/BJ20140620 pubmed: 25017630
Bridges, H. R. et al. Structural basis of mammalian respiratory complex I inhibition by medicinal biguanides. Science 379, 351–357 (2023).
doi: 10.1126/science.ade3332 pubmed: 36701435 pmcid: 7614227
Elgendy, M. et al. Combination of hypoglycemia and metformin impairs tumor metabolic plasticity and growth by modulating the PP2A–GSK3β–MCL-1 axis. Cancer Cell https://doi.org/10.1016/j.ccell.2019.03.007 (2019).
doi: 10.1016/j.ccell.2019.03.007 pubmed: 31031016
To, T.-L. et al. A compendium of genetic modifiers of mitochondrial dysfunction reveals intra-organelle buffering. Cell 179, 1222–1238 (2019).
doi: 10.1016/j.cell.2019.10.032 pubmed: 31730859 pmcid: 7053407
Kim, J. E. et al. Similarities and differences in constipation phenotypes between Lep knockout mice and high fat diet-induced obesity mice. PLoS ONE 17, e0276445 (2022).
doi: 10.1371/journal.pone.0276445 pubmed: 36548335 pmcid: 9778951
Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1031 (2006).
doi: 10.1038/nature05414 pubmed: 17183312
Müller, T. D., Klingenspor, M. & Tschöp, M. H. Revisiting energy expenditure: how to correct mouse metabolic rate for body mass. Nat. Metab. 3, 1134–1136 (2021).
doi: 10.1038/s42255-021-00451-2 pubmed: 34489606
Mina, A. I. et al. CalR: a web-based analysis tool for indirect calorimetry experiments. Cell Metab. 28, 656–666 (2018).
doi: 10.1016/j.cmet.2018.06.019 pubmed: 30017358 pmcid: 6170709
Butler, A. A. & Kozak, L. P. A recurring problem with the analysis of energy expenditure in genetic models expressing lean and obese phenotypes. Diabetes 59, 323–329 (2010).
doi: 10.2337/db09-1471 pubmed: 20103710 pmcid: 2809965
Kuhl, I. et al. POLRMT regulates the switch between replication primer formation and gene expression of mammalian mtDNA. Sci. Adv. 2, e1600963 (2016).
doi: 10.1126/sciadv.1600963 pubmed: 27532055 pmcid: 4975551
Wanrooij, S. et al. Human mitochondrial RNA polymerase primes lagging-strand DNA synthesis in vitro. PNAS 105, 11122–11127 (2008).
doi: 10.1073/pnas.0805399105 pubmed: 18685103 pmcid: 2516254
Gustafsson, C. M., Falkenberg, M. & Larsson, N.-G. Maintenance and expression of mammalian mitochondrial DNA. Annu. Rev. Biochem. 85, 133–160 (2016).
doi: 10.1146/annurev-biochem-060815-014402 pubmed: 27023847
Rath, S. et al. MitoCarta3.0: an updated mitochondrial proteome now with sub-organelle localization and pathway annotations. Nucleic Acids Res. 49, gkaa1011 (2020).
Mourier, A., Ruzzenente, B., Brandt, T., Kühlbrandt, W. & Larsson, N.-G. Loss of LRPPRC causes ATP synthase deficiency. Hum. Mol. Genet. 23, 2580–2592 (2014).
doi: 10.1093/hmg/ddt652 pubmed: 24399447 pmcid: 3990160
Kühl, I. et al. Transcriptomic and proteomic landscape of mitochondrial dysfunction reveals secondary coenzyme Q deficiency in mammals. eLife 6, 1494 (2017).
doi: 10.7554/eLife.30952
Murphy, M. P. & Chouchani, E. T. Why succinate? Physiological regulation by a mitochondrial coenzyme Q sentinel. Nat. Chem. Biol. 18, 461–469 (2022).
doi: 10.1038/s41589-022-01004-8 pubmed: 35484255 pmcid: 9150600
Larsson, N.-G. et al. Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice. Nat. Genet. 18, 231–236 (1998).
doi: 10.1038/ng0398-231 pubmed: 9500544
Rigoulet, M., Mourier, A., Galinier, A., Casteilla, L. & Devin, A. Electron competition process in respiratory chain: Regulatory mechanisms and physiological functions. Biochim. Biophys. Acta Bioenerg. 1797, 671–677 (2010).
doi: 10.1016/j.bbabio.2010.01.030
Molinié, T. et al. MDH2 produced OAA is a metabolic switch rewiring the fuelling of respiratory chain and TCA cycle. Biochim. Biophys. Acta Bioenerg. 1863, 148532 (2022).
doi: 10.1016/j.bbabio.2022.148532 pubmed: 35063410
Kraus, D., Yang, Q. & Kahn, B. Lipid extraction from mouse feces. BIO-Protoc. 5, e1375 (2015).
doi: 10.21769/BioProtoc.1375 pubmed: 27110587
Milenkovic, D. et al. Preserved respiratory chain capacity and physiology in mice with profoundly reduced levels of mitochondrial respirasomes. Cell Metab. https://doi.org/10.1016/j.cmet.2023.07.015 (2023).
doi: 10.1016/j.cmet.2023.07.015 pubmed: 37633273
Mourier, A., Matic, S., Ruzzenente, B., Larsson, N.-G. & Milenkovic, D. The respiratory chain supercomplex organization is independent of COX7a2l isoforms. Cell Metab. 20, 1069–1075 (2014).
doi: 10.1016/j.cmet.2014.11.005 pubmed: 25470551 pmcid: 4261080
Jiang, S. et al. GGPPS‐mediated Rab27A geranylgeranylation regulates β cell dysfunction during type 2 diabetes development by affecting insulin granule docked pool formation. J. Pathol. 238, 109–119 (2016).
doi: 10.1002/path.4652 pubmed: 26434932
Charbord, J. et al. In vivo screen identifies a SIK inhibitor that induces β cell proliferation through a transient UPR. Nat. Metab. 3, 682–700 (2021).
doi: 10.1038/s42255-021-00391-x pubmed: 34031592 pmcid: 9756392
Tyanova, S. & Cox, J. Cancer systems biology, methods and protocols. Methods Mol. Biol. 1711, 133–148 (2018).
doi: 10.1007/978-1-4939-7493-1_7 pubmed: 29344888
Liao, Y., Wang, J., Jaehnig, E. J., Shi, Z. & Zhang, B. WebGestalt 2019: gene set analysis toolkit with revamped UIs and APIs. Nucleic Acids Res. 47, W199–W205 (2019).
doi: 10.1093/nar/gkz401 pubmed: 31114916 pmcid: 6602449
Ahola, S. et al. OMA1-mediated integrated stress response protects against ferroptosis in mitochondrial cardiomyopathy. Cell Metab. 34, 1875–1891 (2022).
doi: 10.1016/j.cmet.2022.08.017 pubmed: 36113464
He, L. et al. Metformin and insulin suppress hepatic gluconeogenesis through phosphorylation of CREB binding protein. Cell 137, 635–646 (2009).
doi: 10.1016/j.cell.2009.03.016 pubmed: 19450513 pmcid: 2775562
Perez-Riverol, Y. et al. The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences. Nucleic Acids Res. 50, D543–D552 (2021).
doi: 10.1093/nar/gkab1038 pmcid: 8728295

Auteurs

Shan Jiang (S)

Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

Taolin Yuan (T)

Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

Florian A Rosenberger (FA)

Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, Germany.

Arnaud Mourier (A)

University of Bordeaux, CNRS, Institut de Biochimie et Génétique Cellulaires (IGBC) UMR, Bordeaux, France.

Nathalia R V Dragano (NRV)

Institute of Experimental Genetics - German Mouse Clinic, Helmholtz Zentrum, Munich, Germany.
German Center for Diabetes Research (DZD), Oberschleißheim-Neuherberg, Neuherberg, Germany.

Laura S Kremer (LS)

Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

Diana Rubalcava-Gracia (D)

Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

Fynn M Hansen (FM)

Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, Germany.

Melissa Borg (M)

Department of Physiology and Pharmacology, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden.

Mara Mennuni (M)

Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

Roberta Filograna (R)

Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

David Alsina (D)

Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

Jelena Misic (J)

Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

Camilla Koolmeister (C)

Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

Polyxeni Papadea (P)

Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

Martin Hrabe de Angelis (MH)

Institute of Experimental Genetics - German Mouse Clinic, Helmholtz Zentrum, Munich, Germany.
German Center for Diabetes Research (DZD), Oberschleißheim-Neuherberg, Neuherberg, Germany.
Chair of Experimental Genetics, TUM School of Life Sciences, Technische Universität München, Freising, Germany.

Lipeng Ren (L)

Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.

Olov Andersson (O)

Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.

Anke Unger (A)

Lead Discovery Center, Dortmund, Germany.

Tim Bergbrede (T)

Lead Discovery Center, Dortmund, Germany.

Raffaella Di Lucrezia (R)

Lead Discovery Center, Dortmund, Germany.

Rolf Wibom (R)

Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden.

Juleen R Zierath (JR)

Department of Physiology and Pharmacology, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden.
Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden.

Anna Krook (A)

Department of Physiology and Pharmacology, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden.

Patrick Giavalisco (P)

Metabolomics Core Facility, Max Planck Institute for Biology of Ageing, Cologne, Germany.

Matthias Mann (M)

Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, Germany.

Nils-Göran Larsson (NG)

Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. nils-goran.larsson@ki.se.

Classifications MeSH