The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
The mitochondrial unfolded protein response–synchronizing genomes
Open accessAbstract
Maintenance of the mitochondrial proteome is performed primarily by chaperones, which fold and assemble proteins, and by proteases, which degrade excess damaged proteins. Upon various types of mitochondrial stress, triggered genetically or pharmacologically, dysfunction of the proteome is sensed and communicated to the nucleus, where an extensive transcriptional program, aimed to repair the damage, is activated. This feedback loop, termed the mitochondrial unfolded protein response (UPR(mt)), synchronizes the activity of the mitochondrial and nuclear genomes and as such ensures the quality of the mitochondrial proteome. Here we review the recent advances in the UPR(mt) field and discuss its induction, signaling, communication with the other mitochondrial and major cellular regulatory pathways, as well as its potential implications on health and lifespan.
Overview
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
Verification
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?
In the citing paper
“On the other hand, multiple cellular stresses associated with the aging process trigger the mitochondrial unfolded protein response (UPRmt) that serves as a critical mechanism for promoting cellular recovery and mitochondrial network survival (68).”
From From mitochondria to sarcopenia: role of 17β-estradiol and testosterone (2023) · cites this paper as [68]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Autophagy and the Integrated Stress Response
Kroemer, G., Mariño, G., & Levine, B. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.023 · Cited by 3,506
Mitochondria: In Sickness and in Health
Nunnari, J., & Suomalainen, A. (2012) · Cell · doi:10.1016/j.cell.2012.02.035 · Cited by 3,479
Sirtuins as regulators of metabolism and healthspan
Houtkooper, R. H., Pirinen, E., & Auwerx, J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3293 · Cited by 2,008
Self-citationA 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
Translocation of Proteins into Mitochondria
Neupert, W., & Herrmann, J. M. (2007) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.052705.163409 · Cited by 1,486
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
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
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
Mitonuclear protein imbalance as a conserved longevity mechanism
Houtkooper, R. H., Mouchiroud, L., Ryu, D., Moullan, N., Katsyuba, E., Knott, G., Williams, R. W., & Auwerx, J. (2013) · Nature · doi:10.1038/nature12188 · Cited by 1,035
Self-citationMitochondrial Import Efficiency of ATFS-1 Regulates Mitochondrial UPR Activation
Nargund, A. M., Pellegrino, M., Fiorese, C. J., Baker, B. M., & Haynes, C. M. (2012) · Science · doi:10.1126/science.1223560 · Cited by 1,027
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
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
ClpP Mediates Activation of a Mitochondrial Unfolded Protein Response in C. elegans
Haynes, C. M., Petrova, K., Benedetti, C., Yang, Y., & Ron, D. (2007) · Developmental Cell · doi:10.1016/j.devcel.2007.07.016 · Cited by 595
Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy
Sentelle, R. D., Senkal, C. E., Jiang, W., Ponnusamy, S., Gencer, S., Panneer Selvam, S., Ramshesh, V. K., Peterson, Y. K., Lemasters, J. J., Szulc, Z. M., et al. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.1059 · Cited by 539
Quality control of mitochondria: protection against neurodegeneration and ageing
Tatsuta, T., & Langer, T. (2008) · The EMBO Journal · doi:10.1038/sj.emboj.7601972 · Cited by 525
The mitochondrial UPR – protecting organelle protein homeostasis
Haynes, C. M., & Ron, D. (2010) · Journal of Cell Science · doi:10.1242/jcs.075119 · Cited by 506
Haynes, C. M., Yang, Y., Blais, S. P., Neubert, T. A., & Ron, D. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.01.015 · Cited by 504
The origin and early evolution of mitochondria.
Gray, M. W., Burger, G., & Lang, B. F. (2001) · Genome biology · doi:10.1186/gb-2001-2-6-reviews1018 · Cited by 483
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
Jin, S. M., & Youle, R. J. (2013) · Autophagy · doi:10.4161/auto.26122 · Cited by 411
Muscle mitohormesis promotes longevity via systemic repression of insulin signaling
Owusu-Ansah, E., Song, W., & Perrimon, N. (2013) · Cell · doi:10.1016/j.cell.2013.09.021 · Cited by 391
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
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
Self-citationRea, S. L., Ventura, N., & Johnson, T. E. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050259 · Cited by 383
Mitochondrial UPR-regulated innate immunity provides resistance to pathogen infection
Pellegrino, M. W., Nargund, A. M., Kirienko, N. V., Gillis, R., Fiorese, C. J., & Haynes, C. M. (2014) · Nature · doi:10.1038/nature13818 · Cited by 378
Benedetti, C., Haynes, C. M., Yang, Y., Harding, H. P., & Ron, D. (2006) · Genetics · doi:10.1534/genetics.106.061580 · Cited by 374
NAD+-Dependent Activation of Sirt1 Corrects the Phenotype in a Mouse Model of Mitochondrial Disease
Cerutti, R., Pirinen, E., Lamperti, C., Marchet, S., Sauve, A. A., Li, W., Leoni, V., Schon, E. A., Dantzer, F., Auwerx, J., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.04.001 · Cited by 343
Selective induction of mitochondrial chaperones in response to loss of the mitochondrial genome.
Martinus, R., Garth, G. P., Webster, T., Cartwright, P., Naylor, D. J., Høj, P., & Hoogenraad, N. (1996) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1996.0098h.x · Cited by 340
Jovaisaite, V., Mouchiroud, L., & Auwerx, J. (2014) · Journal of Experimental Biology · doi:10.1242/jeb.090738 · Cited by 335
Protective Coupling of Mitochondrial Function and Protein Synthesis via the eIF2α Kinase GCN-2
Baker, B. M., Nargund, A. M., Sun, T., & Haynes, C. M. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002760 · Cited by 324
Caenorhabditis elegans pathways that surveil and defend mitochondria
Liu, Y., Samuel, B. S., Breen, P. C., & Ruvkun, G. (2014) · Nature · doi:10.1038/nature13204 · Cited by 309
Aldridge, J. E., Horibe, T., & Hoogenraad, N. J. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000874 · Cited by 299
SirT3 Regulates the Mitochondrial Unfolded Protein Response
Papa, L., & Germain, D. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.01337-13 · Cited by 292
A SIRT7-Dependent Acetylation Switch of GABPβ1 Controls Mitochondrial Function
Ryu, D., Jo, Y. S., Sasso, G. L., Stein, S., Zhang, H., Perino, A., Lee, J. U., Zeviani, M., Romand, R., Hottiger, M. O., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.08.001 · Cited by 267
Pirinen, 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
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
Yokoyama, K., Fukumoto, K., Murakami, T., Harada, S.-I., Hosono, R., Wadhwa, R., Mitsui, Y., & Ohkuma, S. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)02470-5 · Cited by 229
Bennett, C. F., Wende, H. V., Simko, M., Klum, S., Barfield, S., Choi, H., Pineda, V. V., & Kaeberlein, M. R. (2014) · Nature Communications · doi:10.1038/ncomms4483 · Cited by 220
Metabolic networks of longevity
Houtkooper, R. H., Williams, R. W., & Auwerx, J. (2010) · Cell · doi:10.1016/j.cell.2010.06.029 · Cited by 217
Horibe, T., & Hoogenraad, N. J. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000835 · Cited by 215
Rainbolt, T. K., Atanassova, N., Genereux, J. C., & Wiseman, R. L. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.11.006 · Cited by 208
Mitochondrial protein quality control during biogenesis and aging
Baker, B. M., & Haynes, C. M. (2011) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2011.01.004 · Cited by 195
Jeyapaul, J., & Jaiswal, A. K. (2000) · Biochemical Pharmacology · doi:10.1016/s0006-2952(00)00256-2 · Cited by 193
Surveillance-Activated Defenses Block the ROS–Induced Mitochondrial Unfolded Protein Response
Runkel, E. D., Liu, S., Baumeister, R., & Schulze, E. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003346 · Cited by 192
Mitochondrial Genome Content Is Regulated during Nematode Development
Tsang, W. Y. W., & Lemire, B. D. (2002) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2002.6394 · Cited by 187
Lane, N. J. (2011) · BioEssays · doi:10.1002/bies.201100051 · Cited by 183
Mitochondrial Proteostasis in the Control of Aging and Longevity
Jensen, M. B., & Jasper, H. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.05.006 · Cited by 169
Rath, E., Berger, E., Messlik, A., Nunes, T., Liu, B., Kim, S. C., Hoogenraad, N. J., Sans, M., Sartor, R. B., & Haller, D. (2011) · Gut · doi:10.1136/gutjnl-2011-300767 · Cited by 160
Molecular 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
The good and the bad of being connected: the integrons of aging
Dillin, A. G., Gottschling, D. E., & Nyström, T. (2014) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2013.12.003 · Cited by 141
PINK1-Parkin Pathway Activity Is Regulated by Degradation of PINK1 in the Mitochondrial Matrix
Thomas, R. E., Andrews, L. A., Burman, J. L., Lin, W.-Y., & Pallanck, L. J. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004279 · Cited by 134
Rauthan, M., Ranji, P., Pradenas, N. A., Pitot, C., & Pilon, M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1218778110 · Cited by 129
Genetic analysis of mitochondrial protein misfolding in Drosophila melanogaster
Pimenta de Castro, I., Costa, A. C., Lam, D., Tufi, R., Fedele, V, Moisoi, N., Dinsdale, D., Deas, E., Loh, S. H. Y., & Martins, L. M. (2012) · Cell Death & Differentiation · doi:10.1038/cdd.2012.5 · Cited by 128
Complex IV-deficient Surf1−/− mice initiate mitochondrial stress responses
Pulliam, D. A., Deepa, S. S., Liu, Y., Hill, S., Lin, A., Bhattacharya, A., Shi, Y., Sloane, L. B., Viscomi, C. F., Zeviani, M., et al. (2014) · Biochemical Journal · doi:10.1042/bj20140291 · Cited by 111
The paradox of mitochondrial dysfunction and extended longevity
Munkácsy, E., & Rea, S. L. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.03.016 · Cited by 103
Mitochondrial proteolytic stress induced by loss of mortalin function is rescued by Parkin and PINK1
Burbulla, L. F., Fitzgerald, J. C., Stegen, K., Westermeier, J., Thost, A.-K., Kato, H., Mokranjac, D., Sauerwald, J., Martins, L. M., Woitalla, D., et al. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.103 · Cited by 98
TOR Signaling Couples Oxygen Sensing to Lifespan in C. elegans
Schieber, M., & Chandel, N. S. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.08.075 · Cited by 80
Ventura, N., & Rea, S. L. (2007) · Biotechnology Journal · doi:10.1002/biot.200600248 · Cited by 54
Mitochondrial Dysfunction in Aging and Longevity: A Causal or Protective Role?
Pulliam, D. A., Bhattacharya, A., & Remmen, H. V. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4950 · Cited by 34
Guo, B., Huang, X., Zhang, P., Qi, L., Liang, Q., Zhang, X., Huang, J., Fang, B., Hou, W., Han, J., et al. (2014) · The EMBO Reports · doi:10.1002/embr.201338310 · Cited by 34
Flagged first, then by citations
Cited by
Sorted by citations
Kaushik, S., & Cuervo, A. M. (2015) · Nature Medicine · doi:10.1038/nm.4001 · Cited by 899
Mitochondrial quality control and muscle mass maintenance.
Romanello, V., & Sandri, M. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2015.00422 · Cited by 434
The Mitochondrial Basis of Aging and Age-Related Disorders
Srivastava, S. (2017) · Genes · doi:10.3390/genes8120398 · Cited by 446
Repairing 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
The metabolic regulation of aging
Finkel, T. (2015) · Nature Medicine · doi:10.1038/nm.3998 · Cited by 325
Metadata
- Authors
- Jovaisaite, V., & Auwerx, J.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Corresponding author
- Auwerx, Johan
- ORCID
- Auwerx, Johan
- Venue
- Current Opinion in Cell Biology
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 33
- Pages
- 74-81
- ISSN
- 0955-0674 (ISSN-L)
- PMC
- PMC4380587
- OpenAlex
- W2064966129
- Cited by
- 131
- References
- 60
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 6 · 2023: 10 · 2022: 9 · 2021: 7 · 2020: 18 · 2019: 15 · 2018: 14 · 2017: 16 · 2016: 12 · 2015: 13
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- NIH (R01AG043930)
- SNSF (31003A-140780)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- mitochondrial unfolded protein response, mitochondrial proteome, mitochondrial stress, mitochondrial chaperone, mitochondrial protease, mitochondrial-nuclear communication, transcriptional regulation, lifespan, mitochondrial dysfunction
- MeSH terms
- Aging, Animals, Cell Nucleus, Humans, Mammals, Mitochondria, Signal Transduction, Genome, Cytoprotection, Proteome, Mitochondrial Proteins, Genome, Mitochondrial, 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
