Mitonuclear protein imbalance as a conserved longevity mechanism
Open accessAbstract
Longevity is regulated by a network of closely linked metabolic systems. We used a combination of mouse population genetics and RNA interference in Caenorhabditis elegans to identify mitochondrial ribosomal protein S5 (Mrps5) and other mitochondrial ribosomal proteins as metabolic and longevity regulators. MRP knockdown triggers mitonuclear protein imbalance, reducing mitochondrial respiration and activating the mitochondrial unfolded protein response. Specific antibiotics targeting mitochondrial translation and ethidium bromide (which impairs mitochondrial DNA transcription) pharmacologically mimic mrp knockdown and extend worm lifespan by inducing mitonuclear protein imbalance, a stoichiometric imbalance between nuclear and mitochondrially encoded proteins. This mechanism was also conserved in mammalian cells. In addition, resveratrol and rapamycin, longevity compounds acting on different molecular targets, similarly induced mitonuclear protein imbalance, the mitochondrial unfolded protein response and lifespan extension in C. elegans. Collectively these data demonstrate that MRPs represent an evolutionarily conserved protein family that ties the mitochondrial ribosome and mitonuclear protein imbalance to the mitochondrial unfolded protein response, an overarching longevity pathway across many species.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A disturbed balance between nuclear DNA-encoded and mtDNA-encoded OXPHOS proteins, independent of mitochondrial content, has previously been associated with activation of mitochondrial quality control mechanisms such as the mtUPR.
“A disturbed balance between the nuclear DNA-encoded and mitochondrial DNA (mtDNA)-encoded OXPHOS proteins, independent of mitochondrial content, has previously been associated with the activation of mitochondrial quality control mechanisms such as the mtUPR [32, 33].”
From Human skeletal muscle mitochondrial dynamics in relation to oxidative capacity and insulin sensitivity (2021) · cites this paper as [32]
Activation of the mtUPR is beneficial for cellular function and organism longevity.
“suggesting that an activation of the mtUPR is beneficial for cellular function and organism longevity.”
From Human skeletal muscle mitochondrial dynamics in relation to oxidative capacity and insulin sensitivity (2021) · cites this paper as [32]
An alteration in the balance between nuclear and mtDNA-encoded OXPHOS complexes (mitonuclear protein imbalance) is a stressor to mitochondria.
“an alteration in the balance between nuclear and mtDNA-encoded OXPHOS complexes, the so-called mitonuclear protein imbalance, is a stressor to mitochondria [32].”
From Human skeletal muscle mitochondrial dynamics in relation to oxidative capacity and insulin sensitivity (2021) · cites this paper as [32]
More mitochondrial translation without a change in cytosolic translation can cause mitonuclear protein imbalance.
“Increased mitochondrial translation, without according changes in cytosolic translation rates, can lead to mitonuclear protein imbalance (Houtkooper et al., 2013), which was evidenced by altered protein ratios between MTCO1, which is encoded by mtDNA, and SDHA, encoded by nDNA, induced by MRL-45696 (Figures 3E and 3F).”
From Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle (2014) · cites this paper as Houtkooper et al., 2013
MRL-45696 produced altered MTCO1/SDHA protein ratios, indicating mitonuclear protein imbalance.
“Increased mitochondrial translation, without according changes in cytosolic translation rates, can lead to mitonuclear protein imbalance (Houtkooper et al., 2013), which was evidenced by altered protein ratios between MTCO1, which is encoded by mtDNA, and SDHA, encoded by nDNA, induced by MRL-45696 (Figures 3E and 3F).”
From Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle (2014) · cites this paper as Houtkooper et al., 2013
Such mitonuclear protein imbalance could trigger UPRmt to restore optimal mitochondrial function.
“Such a mitonuclear protein imbalance could trigger UPRmt to restore optimal mitochondrial function (Houtkooper et al., 2013).”
From Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle (2014) · cites this paper as Houtkooper et al., 2013
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Sequence and organization of the human mitochondrial genome
Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., et al. (1981) · Nature · doi:10.1038/290457a0 · Cited by 9,640 · see citing works
Lagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., Messadeq, N., Milne, J., Lambert, P., Elliott, P., et al. (2006) · Cell · doi:10.1016/j.cell.2006.11.013 · Cited by 4,057 · see citing works
Self-citationRapamycin fed late in life extends lifespan in genetically heterogeneous mice
Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., et al. (2009) · Nature · doi:10.1038/nature08221 · Cited by 3,766 · see citing works
A C. elegans mutant that lives twice as long as wild type
Kenyon, C., Chang, J., Gensch, E., Rudner, A., & Tabtiang, R. (1993) · Nature · doi:10.1038/366461a0 · Cited by 3,387 · see citing works
Open source clustering software
de Hoon, M., Imoto, S., Nolan, J., & Miyano, S. (2004) · Bioinformatics · doi:10.1093/bioinformatics/bth078 · Cited by 3,043 · see citing works
Extending Healthy Life Span—From Yeast to Humans
Fontana, L., Partridge, L., & Longo, V. D. (2010) · Science · doi:10.1126/science.1172539 · Cited by 3,023 · see citing works
Kenyon, C. J. (2010) · Nature · doi:10.1038/nature08980 · Cited by 2,739 · see citing works
Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation
Watanabe, M., Houten, S. M., Mataki, C., Christoffolete, M. A., Kim, B. W., Sato, H., Messaddeq, N., Harney, J. W., Ezaki, O., Kodama, T., et al. (2006) · Nature · doi:10.1038/nature04330 · Cited by 2,220 · see citing works
Self-citationReich, M. M., Liefeld, T., Gould, J., Lerner, J., Tamayo, P., & Mesirov, J. P. (2006) · Nature Genetics · doi:10.1038/ng0506-500 · Cited by 2,035 · see citing works
A Mitochondrial Protein Compendium Elucidates Complex I Disease Biology
Pagliarini, D. J., Calvo, S. E., Chang, B., Sheth, S. A., Vafai, S. B., Ong, S.-E., Walford, G. A., Sugiana, C., Boneh, A., Chen, W. K., et al. (2008) · Cell · doi:10.1016/j.cell.2008.06.016 · Cited by 1,994 · see citing works
Sirtuin activators mimic caloric restriction and delay ageing in metazoans
Wood, J. G., Rogina, B., Lavu, S., Howitz, K., Helfand, S. L., Tatar, M., & Sinclair, D. (2004) · Nature · doi:10.1038/nature02789 · Cited by 1,868 · see citing works
Mouse genomic variation and its effect on phenotypes and gene regulation.
Keane, T. M., Goodstadt, L., Danecek, P., White, M. A., Wong, K., Yalcin, B., Heger, A., Agam, A., Slater, G., Goodson, M., et al. (2011) · Nature · doi:10.1038/nature10413 · Cited by 1,580 · see citing works
Supercomplexes in the respiratory chains of yeast and mammalian mitochondria
Schägger, H., & Pfeiffer, K. (2000) · The EMBO Journal · doi:10.1093/emboj/19.8.1777 · Cited by 1,356 · see citing works
Kamath, R. S., Martinez-Campos, M., Zipperlen, P., Fraser, A. G., & Ahringer, J. (2000) · Genome biology · doi:10.1186/gb-2000-2-1-research0002 · Cited by 1,315 · see citing works
Schulz, T. J., Zarse, K., Voigt, A., Urban, N., Birringer, M., & Ristow, M. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.08.011 · Cited by 1,209 · see citing works
Rates of Behavior and Aging Specified by Mitochondrial Function During Development
Dillin, A., Hsu, A.-L., Arantes-Oliveira, N., Lehrer-Graiwer, J., Hsin, H., Fraser, A. G., Kamath, R. S., Ahringer, J., & Kenyon, C. (2002) · Science · doi:10.1126/science.1077780 · Cited by 1,121 · see citing works
The Cell Non-Autonomous Nature of Electron Transport Chain-Mediated Longevity
Durieux, J., Wolff, S., & Dillin, A. (2011) · Cell · doi:10.1016/j.cell.2010.12.016 · Cited by 1,059 · see citing works
A mitochondrial specific stress response in mammalian cells
Zhao, Q., Wang, J., Levichkin, I. V., Stasinopoulos, S., Ryan, M. T., & Hoogenraad, N. J. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf445 · Cited by 1,026 · see citing works
A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity
Lee, S. S., Lee, R. Y. N., Fraser, A. G., Kamath, R. S., Ahringer, J., & Ruvkun, G. (2003) · Nature Genetics · doi:10.1038/ng1056 · Cited by 969 · see citing works
The genetics of caloric restriction in Caenorhabditis elegans
Lakowski, B., & Hekimi, S. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.22.13091 · Cited by 967 · see citing works
Variations in DNA elucidate molecular networks that cause disease
Chen, Y., Zhu, J., Lum, P. Y., Yang, X., Pinto, S., MacNeil, D. J., Zhang, C., Lamb, J., Edwards, S., Sieberts, S. K., et al. (2008) · Nature · doi:10.1038/nature06757 · Cited by 887 · see citing works
TOR Signaling and Rapamycin Influence Longevity by Regulating SKN-1/Nrf and DAF-16/FoxO
Robida-Stubbs, S., Glover-Cutter, K., Lamming, D. W., Mizunuma, M., Narasimhan, S. D., Neumann-Haefelin, E., Sabatini, D. M., & Blackwell, T. K. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.007 · Cited by 648 · see citing works
Yoneda, T., Benedetti, C., Urano, F., Clark, S. G., Harding, H. P., & Ron, D. (2004) · Journal of Cell Science · doi:10.1242/jcs.01275 · Cited by 636 · see citing works
A Mitochondrial Superoxide Signal Triggers Increased Longevity in Caenorhabditis elegans
Yang, W., & Hekimi, S. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000556 · Cited by 630 · see citing works
Aging and Survival: The Genetics of Life Span Extension by Dietary Restriction
Mair, W. B., & Dillin, A. G. (2008) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.77.061206.171059 · Cited by 600 · see citing works
4E-BP Extends Lifespan upon Dietary Restriction by Enhancing Mitochondrial Activity in Drosophila
Zid, B. M., Rogers, A. N., Katewa, S. D., Vargas, M. A., Kolipinski, M., Lu, T. A., Benzer, S., & Kapahi, P. (2009) · Cell · doi:10.1016/j.cell.2009.07.034 · Cited by 541 · see citing works
Hansen, M., Hsu, A., Dillin, A. G., & Kenyon, C. J. (2005) · PLoS Genetics · doi:10.1371/journal.pgen.0010017 · Cited by 533 · see citing works
A systematic RNAi screen for longevity genes in C. elegansPreprint
Hamilton, B., Dong, Y., Shindo, M., Liu, W., Odell, I., Ruvkun, G., & Lee, S. S. (2005) · Genes & Development · doi:10.1101/gad.1308205 · Cited by 513 · see citing works
Liao, C., Rikke, B. A., Johnson, T. E., Diaz, V., & Nelson, J. F. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2009.00533.x · Cited by 501 · see citing works
A new set of BXD recombinant inbred lines from advanced intercross populations in mice
Peirce, J. L., Lu, L., Gu, J., Silver, L. M., & Williams, R. W. (2004) · BMC Genetics · doi:10.1186/1471-2156-5-7 · Cited by 494 · see citing works
Self-citationThe mitochondrial UPR – protecting organelle protein homeostasis
Haynes, C. M., & Ron, D. (2010) · Journal of Cell Science · doi:10.1242/jcs.075119 · Cited by 490 · see citing works
Haynes, C. M., Yang, Y., Blais, S., Neubert, T., & Ron, D. (2010) · Molecules and Cells · doi:10.1016/j.molcel.2010.01.015 · Cited by 480 · see citing works
Zarse, K., Schmeisser, S., Groth, M., Priebe, S., Beuster, G., Kuhlow, D., Guthke, R., Platzer, M., Kahn, C. R., & Ristow, M. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.02.013 · Cited by 430 · see citing works
Mutations in the clk-1 gene of Caenorhabditis elegans affect developmental and behavioral timing
Wong, A., Boutis, P., & Hekimi, S. (1995) · Genetics · doi:10.1093/genetics/139.3.1247 · Cited by 416 · see citing works
Benedetti, C., Haynes, C. M., Yang, Y., Harding, H. P., & Ron, D. (2006) · Genetics · doi:10.1534/genetics.106.061580 · Cited by 382 · see citing works
Sharma, M. R., Koc, E., Datta, P., Booth, T. M., Spremulli, L., & Agrawal, R. (2003) · Cell · doi:10.1016/s0092-8674(03)00762-1 · Cited by 373 · see citing works
Selective inhibition of the synthesis of mitochondria-associated RNA by ethidium bromide
Zylbee, E., Vesco, C., & Penman, S. (1969) · Journal of Molecular Biology · doi:10.1016/0022-2836(69)90414-8 · Cited by 312 · see citing works
A High-Resolution Single Nucleotide Polymorphism Genetic Map of the Mouse Genome
Shifman, S., Bell, J. T., Copley, R. R., Taylor, M. S., Williams, R. W., Mott, R., & Jonathan Flint, C. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040395 · Cited by 269 · see citing works
Self-citationAndreux, P. A., Williams, E. G., Koutníková, H., Houtkooper, R. H., Champy, M., Henry, H., Schoonjans, K., Williams, R. W., & Auwerx, J. H. (2012) · Cell · doi:10.1016/j.cell.2012.08.012 · Cited by 229 · see citing works
Self-citationMetabolic networks of longevity
Houtkooper, R. H., Williams, R. W., & Auwerx, J. (2010) · Cell · doi:10.1016/j.cell.2010.06.029 · Cited by 217 · see citing works
Gene expression profiling of aging reveals activation of a p53-mediated transcriptional program
Edwards, M. G., Anderson, R. M., Yuan, M., Kendziorski, C. M., Weindruch, R., & Prolla, T. A. (2007) · BMC Genomics · doi:10.1186/1471-2164-8-80 · Cited by 174 · see citing works
CREB and ChREBP oppositely regulate SIRT1 expression in response to energy availability
Noriega, L. G., Feige, J. N., Cantó, C., Yamamoto, H., Yu, J., Herman, M. A., Mataki, C., Kahn, B. B., & Auwerx, J. H. (2011) · EMBO Reports · doi:10.1038/embor.2011.151 · Cited by 172 · see citing works
Self-citationGene expression in the mouse eye: an online resource for genetics using 103 strains of mice.
Geisert, E. E., Lu, L., Freeman-Anderson, N. E., et al. (2009) · PubMed · Cited by 92 · see citing works
Mouchiroud, L., Molin, L., Kasturi, P., Triba, M. N., Dumas, M., Wilson, M. C., Halestrap, A. P., Roussel, D., Masse, I., Dallière, N., et al. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00640.x · Cited by 90 · see citing works
Self-citationde Haan, G., & van Zant, G. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.6.707 · Cited by 87 · see citing works
Overall, R. W. (2009) · Frontiers in Neuroscience · doi:10.3389/neuro.15.003.2009 · Cited by 72 · see citing works
Endoplasmic Reticulum Stress Promotes LIPIN2-Dependent Hepatic Insulin Resistance
Ryu, D., Seo, W., Yoon, Y.-S., Kim, Y.-N., Kim, S. S., Kim, H., Park, T., Choi, C. S., & Koo, S. (2011) · Diabetes · doi:10.2337/db10-1046 · Cited by 61 · see citing works
Self-citationMouse phenogenomics: the fast track to “systems metabolism
Argmann, C. A., Chambon, P., & Auwerx, J. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.11.002 · Cited by 51 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Mitophagy and Quality Control Mechanisms in Mitochondrial Maintenance
Pickles, S., Vigié, P., & Youle, R. J. (2018) · Current Biology · doi:10.1016/j.cub.2018.01.004 · Cited by 2,081 · see citing works
Sarcopenia: Aging-Related Loss of Muscle Mass and Function
Larsson, L., Degens, H., Li, M., Salviati, L., Lee, Y. I., Thompson, W., Kirkland, J. L., & Sandri, M. (2019) · Physiological Reviews · doi:10.1152/physrev.00061.2017 · Cited by 1,797 · see citing works
Mitochondrial form and function
Friedman, J. R., & Nunnari, J. (2014) · Nature · doi:10.1038/nature12985 · Cited by 1,803 · see citing works
Cantó, C., Menzies, K. J., & Auwerx, J. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.023 · Cited by 1,648 · see citing works
Self-citationGomes, A. P., Price, N. L., Ling, A. J. Y., Moslehi, J. J., Montgomery, M. K., Rajman, L., White, J. P., Teodoro, J. S., Wrann, C. D., Hubbard, B. P., et al. (2013) · Cell · doi:10.1016/j.cell.2013.11.037 · Cited by 1,482 · see citing works
The mitochondrial basis of aging
Sun, N., Youle, R. J., & Finkel, T. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.01.028 · Cited by 1,441 · see citing works
From discoveries in ageing research to therapeutics for healthy ageing
Campisi, J., Kapahi, P., Lithgow, G. J., Melov, S., Newman, J. C., & Verdin, E. (2019) · Nature · doi:10.1038/s41586-019-1365-2 · Cited by 1,389 · see citing works
Mouchiroud, L., Houtkooper, R. H., Moullan, N., Katsyuba, E., Ryu, D., Cantó, C., Mottis, A., Jo, Y.-S., Viswanathan, M., Schoonjans, K., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.016 · Cited by 1,210 · see citing works
Self-citationRyu, D., Mouchiroud, L., Andreux, P. A., Katsyuba, E., Moullan, N., Nicolet-dit-Félix, A. A., Williams, E. G., Jha, P., Lo Sasso, G., Huzard, D., et al. (2016) · Nature Medicine · doi:10.1038/nm.4132 · Cited by 1,105 · see citing works
Self-citationEpigenetic mechanisms of longevity and aging
Sen, P., Shah, P. P., Nativio, R., & Berger, S. L. (2016) · Cell · doi:10.1016/j.cell.2016.07.050 · Cited by 956 · see citing works
Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., Redpath, P., Migaud, M. E., Apte, R. S., Uchida, K., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.013 · Cited by 930 · see citing works
Quirós, P. M., Prado, M. A., Zamboni, N., D’Amico, D., Williams, R. W., Finley, D., Gygi, S. P., & Auwerx, J. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201702058 · Cited by 832 · see citing works
Self-citationMitonuclear communication in homeostasis and stress
Quirós, P. M., Mottis, A., & Auwerx, J. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.23 · Cited by 787 · see citing works
Self-citationThe transcriptional landscape of age in human peripheral blood
Peters, M. J., Joehanes, R., Pilling, L. C., Schurmann, C., Conneely, K. N., Powell, J., Reinmaa, E., Sutphin, G. L., Zhernakova, A., Schramm, K., et al. (2015) · Nature Communications · doi:10.1038/ncomms9570 · Cited by 725 · see citing works
Enhancing mitochondrial proteostasis reduces amyloid-β proteotoxicity
Sorrentino, V., Romani, M., Mouchiroud, L., Beck, J. S., Zhang, H., D’Amico, D., Moullan, N., Potenza, F., Schmid, A. W., Rietsch, S., et al. (2017) · Nature · doi:10.1038/nature25143 · Cited by 630 · see citing works
Self-citationJones, D. P., & Sies, H. (2015) · Antioxidants & Redox Signaling · doi:10.1089/ars.2015.6247 · Cited by 647 · see citing works
Yun, J., & Finkel, T. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.01.011 · Cited by 626 · see citing works
Mitochondria as signaling organelles
Chandel, N. S. (2014) · BMC Biology · doi:10.1186/1741-7007-12-34 · Cited by 576 · see citing works
Disease tolerance and immunity in host protection against infection
Soares, M. P., Teixeira, L., & Moita, L. F. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2016.136 · Cited by 376 · see citing works
It takes two to tango: NAD(+) and sirtuins in aging/longevity control
Imai, S.-I., & Guarente, L. (2016) · npj Aging and Mechanisms of Disease · doi:10.1038/npjamd.2016.17 · Cited by 394 · see citing works
Mistimed sleep disrupts circadian regulation of the human transcriptome
Archer, S. N., Laing, E. E., Möller-Levet, C. S., van der Veen, D. R., Bucca, G., Lazar, A. S., Santhi, N., Slak, A., Kabiljo, R., von Schantz, M., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1316335111 · Cited by 386 · see citing works
Nuclear DNA damage signalling to mitochondria in ageing
Fang, E. F., Scheibye-Knudsen, M., Chua, K. F., Mattson, M. P., Croteau, D. L., & Bohr, V. A. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.14 · Cited by 387 · see citing works
Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3
Khan, N. A., Auranen, M., Paetau, I., Pirinen, E., Euro, L., Forsström, S., Pasila, L., Velagapudi, V., Carroll, C. J., Auwerx, J., et al. (2014) · EMBO Molecular Medicine · doi:10.1002/emmm.201403943 · Cited by 385 · see citing works
Self-citationTwo conserved histone demethylases regulate mitochondrial stress-induced longevity
Merkwirth, C., Jovaisaite, V., Durieux, J., Matilainen, O., Jordan, S. D., Quiros, P. M., Steffen, K. K., Williams, E. G., Mouchiroud, L., Tronnes, S. U., et al. (2016) · Cell · doi:10.1016/j.cell.2016.04.012 · Cited by 363 · see citing works
Self-citationPharmacological approaches to restore mitochondrial function
Andreux, P. A., Houtkooper, R. H., & Auwerx, J. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4023 · Cited by 383 · see citing works
Self-citationDietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling
Weir, H. J., Yao, P., Huynh, F. K., Escoubas, C. C., Goncalves, R. L., Burkewitz, K., Laboy, R., Hirschey, M. D., & Mair, W. B. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.09.024 · Cited by 372 · see citing works
Gariani, K., Menzies, K. J., Ryu, D., Wegner, C. J., Wang, X., Ropelle, E. R., Moullan, N., Zhang, H., Perino, A., Lemos, V., et al. (2016) · Hepatology · doi:10.1002/hep.28245 · Cited by 368 · see citing works
Self-citationThe role of mitochondria in aging
Jang, J. Y., Blum, A., Liu, J., & Finkel, T. (2018) · Journal of Clinical Investigation · doi:10.1172/jci120842 · Cited by 358 · see citing works
Migliavacca, E., Tay, S. K. H., Patel, H. P., Sonntag, T., Civiletto, G., McFarlane, C., Forrester, T., Barton, S. J., Leow, M. K., Antoun, E., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13694-1 · Cited by 365 · see citing works
Growth differentiation factor 15 is a myomitokine governing systemic energy homeostasis
Chung, H. K., Ryu, D., Kim, K. S., Chang, J. Y., Kim, Y. K., Yi, H.-S., Kang, S. G., Choi, M. J., Lee, S. E., Jung, S.-B., et al. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201607110 · Cited by 357 · see citing works
Self-citationMetformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2
De Haes, W., Frooninckx, L., Van Assche, R., Smolders, A., Depuydt, G., Billen, J., Braeckman, B. P., Schoofs, L., & Temmerman, L. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1321776111 · Cited by 355 · see citing works
Mechanisms and regulation of protein synthesis in mitochondria
Kummer, E., & Ban, N. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00332-2 · Cited by 349 · see citing works
Jovaisaite, V., Mouchiroud, L., & Auwerx, J. (2014) · Journal of Experimental Biology · doi:10.1242/jeb.090738 · Cited by 335 · see citing works
Self-citationRepairing mitochondrial dysfunction in disease
Sorrentino, V., Menzies, K. J., & Auwerx, J. (2018) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010716-104908 · Cited by 337 · see citing works
The metabolic regulation of aging
Finkel, T. (2015) · Nature Medicine · doi:10.1038/nm.3998 · Cited by 325 · see citing works
Rana, A., Oliveira, M. P., Khamoui, A. V., Aparicio, R., Rera, M., Rossiter, H. B., & Walker, D. W. (2017) · Nature Communications · doi:10.1038/s41467-017-00525-4 · Cited by 294 · see citing works
Multilayered Genetic and Omics Dissection of Mitochondrial Activity in a Mouse Reference Population
Wu, Y., Williams, E. G., Dubuis, S., Mottis, A., Jovaisaite, V., Houten, S. M., Argmann, C. A., Faridi, P., Wolski, W., Kutalik, Z., et al. (2014) · Cell · doi:10.1016/j.cell.2014.07.039 · Cited by 244 · see citing works
Self-citationPirinen, E., Cantó, C., Jo, Y. S., Morato, L., Zhang, H., Menzies, K. J., Williams, E. G., Mouchiroud, L., Moullan, N., Hagberg, C., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.04.002 · Cited by 254 · see citing works
“Such a mitonuclear protein imbalance could trigger UPRmt to restore optimal mitochondrial function (Houtkooper et al., 2013).”
BackgroundInfluentialSelf-citationVannini, N., Campos, V., Girotra, M., Trachsel, V., Rojas-Sutterlin, S., Tratwal, J., Ragusa, S., Stefanidis, E., Ryu, D., Rainer, P. Y., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.02.012 · Cited by 218 · see citing works
Self-citationReproducibility and replicability of rodent phenotyping in preclinical studies
Kafkafi, N., Agassi, J., Chesler, E. J., Crabbe, J. C., Crusio, W. E., Eilam, D., Gerlai, R., Golani, I., Gomez-Marin, A., Heller, R., et al. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.01.003 · Cited by 215 · see citing works
Self-citationProteostasis collapse is a driver of cell aging and death
Santra, M., Dill, K. A., & de Graff, A. M. R. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1906592116 · Cited by 175 · see citing works
The RNA-Binding Protein PUM2 Impairs Mitochondrial Dynamics and Mitophagy During Aging
D’Amico, D., Mottis, A., Potenza, F., Sorrentino, V., Li, H., Romani, M., Lemos, V., Schoonjans, K., Zamboni, N., Knott, G., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2018.11.034 · Cited by 159 · see citing works
Self-citationMolecular mechanisms underlying genotype‐dependent responses to dietary restriction
Schleit, J., Johnson, S. C., Bennett, C. F., Simko, M., Trongtham, N., Castanza, A., Hsieh, E. J., Moller, R. M., Wasko, B. M., Delaney, J. R., et al. (2013) · Aging Cell · doi:10.1111/acel.12130 · Cited by 159 · see citing works
New mechanisms of metformin action: Focusing on mitochondria and the gut
Hur, K. Y., & Lee, M. (2015) · Journal of Diabetes Investigation · doi:10.1111/jdi.12328 · Cited by 161 · see citing works
Signaling networks determining life span
Riera, C. E., Merkwirth, C., De Magalhaes Filho, C. D., & Dillin, A. (2016) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014451 · Cited by 161 · see citing works
Blakney, A. K., Zhu, Y., McKay, P. F., Bouton, C. R., Yeow, J., Tang, J., Hu, K., Samnuan, K., Grigsby, C. L., Shattock, R. J., et al. (2020) · ACS Nano · doi:10.1021/acsnano.0c00326 · Cited by 155 · see citing works
Tipping the metabolic scales towards increased longevity in mammals
Riera, C. E., & Dillin, A. (2015) · Nature Cell Biology · doi:10.1038/ncb3107 · Cited by 153 · see citing works
Transcriptional Signatures of Aging
Stegeman, R., & Weake, V. M. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.06.019 · Cited by 146 · see citing works
van de Weijer, T., Phielix, E., Bilet, L., Williams, E. G., Ropelle, E. R., Bierwagen, A., Livingstone, R., Nowotny, P., Sparks, L. M., Paglialunga, S., et al. (2015) · Diabetes · doi:10.2337/db14-0667 · Cited by 139 · see citing works
Self-citationDietary restriction.; mitochondrial function and aging: From yeast to humans
Ruetenik, A., & Barrientos, A. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.05.005 · Cited by 139 · see citing works
The mitochondrial unfolded protein response–synchronizing genomes
Jovaisaite, V., & Auwerx, J. (2015) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2014.12.003 · Cited by 131 · see citing works
Bezawork-Geleta, A., Brodie, E. J., Dougan, D. A., & Truscott, K. N. (2015) · Scientific Reports · doi:10.1038/srep17397 · Cited by 113 · see citing works
The mitochondrial unfolded protein response and mitohormesis: a perspective on metabolic diseases
Yi, H.-S., Chang, J. Y., & Shong, M. (2018) · Journal of Molecular Endocrinology · doi:10.1530/jme-18-0005 · Cited by 99 · see citing works
NAD+ boosting reduces age-associated amyloidosis and restores mitochondrial homeostasis in muscle
Romani, M., Sorrentino, V., Oh, C.-M., Li, H., de Lima, T. I., Zhang, H., Shong, M., & Auwerx, J. (2021) · Cell Reports · doi:10.1016/j.celrep.2020.108660 · Cited by 92 · see citing works
Self-citationDeepa, S. S., Bhaskaran, S., Ranjit, R., Qaisar, R., Nair, B. C., Liu, Y., Walsh, M. E., Fok, W. C., & Van Remmen, H. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.12.021 · Cited by 93 · see citing works
Houzelle, A., Jörgensen, J. A., Schaart, G., Daemen, S., van Polanen, N., Fealy, C. E., Hesselink, M. K. C., Schrauwen, P., & Hoeks, J. (2021) · Diabetologia · doi:10.1007/s00125-020-05335-w · Cited by 83 · see citing works
Species comparison of liver proteomes reveals links to naked mole-rat longevity and human aging
Heinze, I., Bens, M., Calzia, E., Holtze, S., Dakhovnik, O., Sahm, A., Kirkpatrick, J. M., Szafranski, K., Romanov, N., Sama, S. N., et al. (2018) · BMC Biology · doi:10.1186/s12915-018-0547-y · Cited by 65 · see citing works
Sensing the Stress: A Role for the UPRmt and UPRam in the Quality Control of Mitochondria
Callegari, S., & Dennerlein, S. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00031 · Cited by 58 · see citing works
C. elegans as a model organism for human mitochondrial associated disorders
Maglioni, S., & Ventura, N. (2016) · Mitochondrion · doi:10.1016/j.mito.2016.02.003 · Cited by 54 · see citing works
The role of mitochondria in <scp>mTOR</scp>‐regulated longevity
Wei, Y., Zhang, Y., Cai, Y., & Xu, M. (2015) · Biological Reviews · doi:10.1111/brv.12103 · Cited by 56 · see citing works
Adams, V., Bowen, T. S., Werner, S., Barthel, P., Amberger, C., Konzer, A., Graumann, J., Sehr, P., Lewis, J., Provaznik, J., et al. (2019) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.12448 · Cited by 51 · see citing works
Mitochondrial Chaperones in the Brain: Safeguarding Brain Health and Metabolism?
Castro, J. P., Wardelmann, K., Grune, T., & Kleinridders, A. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00196 · Cited by 53 · see citing works
Oxidative Status Predicts Quality in Human Mesenchymal Stem Cells
Bertolo, A., Capossela, S., Fränkl, G., Baur, M., Pötzel, T., & Stoyanov, J. (2017) · Stem Cell Research & Therapy · doi:10.1186/s13287-016-0452-7 · Cited by 36 · see citing works
A Genetic Screen Identifies Hypothalamic Fgf15 as a Regulator of Glucagon Secretion
Picard, A., Soyer, J., Berney, X., Tarussio, D., Quenneville, S., Jan, M., Grouzmann, E., Burdet, F., Ibberson, M., & Thorens, B. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.10.041 · Cited by 35 · see citing works
Metabolic mechanisms of species-specific developmental tempo
Iwata, R., & Vanderhaeghen, P. (2024) · Developmental Cell · doi:10.1016/j.devcel.2024.05.027 · Cited by 32 · see citing works
Integrating ER and Mitochondrial Proteostasis in the Healthy and Diseased Heart
Arrieta, A., Blackwood, E. A., Stauffer, W. T., & Glembotski, C. C. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2019.00193 · Cited by 27 · see citing works
Zhou, H., Yuan, D., Gao, W., Tian, J., Sun, H., Yu, S., Wang, J., & Sun, L. (2020) · IUBMB Life · doi:10.1002/iub.2289 · Cited by 22 · see citing works
Mulvey, L., Sands, W. A., Salin, K., Carr, A. E., & Selman, C. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.09.001 · Cited by 16 · see citing works
Collaboration between mitochondria and the nucleus is key to long life in Caenorhabditis elegans
Chang, H.-W., Shtessel, L., & Lee, S. S. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.10.576 · Cited by 15 · see citing works
- Authors
- Houtkooper, R. H., Mouchiroud, L., Ryu, D., Moullan, N., Katsyuba, E., Knott, G., Williams, R. W., & Auwerx, J.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Corresponding author
- Auwerx, Johan
- ORCID
- Venue
- Nature
- Published
- 2013-05-22
- Volume
- 497
- Issue
- 7450
- Pages
- 451-457
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3663447
- OpenAlex
- W2032022203
- Cited by
- 1,035
- References
- 48
- Citations by year
- 2026: 58 · 2025: 63 · 2024: 83 · 2023: 65 · 2022: 93 · 2021: 100 · 2020: 82 · 2019: 66 · 2018: 82 · 2017: 73 · 2016: 87 · 2015: 82 · 2014: 73 · 2013: 27
- FWCI
- 31.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Pure Amsterdam UMC (submittedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (U01AA14425, U01AA013499, UO1AA13499, U01AA014425)
- National Institute on Aging (R01AG043930)
- National Institute on Drug Abuse (P20 DA 21131, P20DA021131)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- longevity, mitochondrial ribosomal proteins, mitochondrial unfolded protein response, mitochondrial respiration, lifespan extension, mitochondrial translation, ethidium bromide, resveratrol, rapamycin, BXD mouse strains, Caenorhabditis elegans
- MeSH terms
- Aging, Animals, Anti-Bacterial Agents, Doxycycline, Female, Longevity, Male, Mice, Inbred Strains, Mitochondria, Ribosomal Proteins, Reproducibility of Results, Caenorhabditis elegans, Evolution, Molecular, Sirolimus, Mitochondrial Proteins, Caenorhabditis elegans Proteins, RNA Interference, Quantitative Trait Loci, Mice, Unfolded Protein Response
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
