The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Targeted Expression of Catalase to Mitochondria Prevents Age-Associated Reductions in Mitochondrial Function and Insulin Resistance
Open accessAbstract
Aging-associated muscle insulin resistance has been hypothesized to be due to decreased mitochondrial function, secondary to cumulative free radical damage, leading to increased intramyocellular lipid content. To directly test this hypothesis, we examined both in vivo and in vitro mitochondrial function, intramyocellular lipid content, and insulin action in lean healthy mice with targeted overexpression of the human catalase gene to mitochondria (MCAT mice). Here, we show that MCAT mice are protected from age-induced decrease in muscle mitochondrial function (∼30%), energy metabolism (∼7%), and lipid-induced muscle insulin resistance. This protection from age-induced reduction in mitochondrial function was associated with reduced mitochondrial oxidative damage, preserved mitochondrial respiration and muscle ATP synthesis, and AMP-activated protein kinase-induced mitochondrial biogenesis. Taken together, these data suggest that the preserved mitochondrial function maintained by reducing mitochondrial oxidative damage may prevent age-associated whole-body energy imbalance and muscle insulin resistance.
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In the citing paper
“Dysfunctional mitochondria accumulate with age, best documented in tissues comprised largely of post-mitotic cells”
From Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype (2016) · cites this paper as Lee et al., 2010
Experimental — accuracy not yet measuredIn the citing paper
“genetic or pharmacological manipulations that lowered mitochondrial ROS production preserved insulin action in lipid-treated myotubes (Hoehn et al., 2009) and in mice fed a high fat diet (Anderson et al., 2009; Hoehn et al., 2009; Lee et al., 2010).”
From Lipid-Induced Mitochondrial Stress and Insulin Action in Muscle (2012) · cites this paper as Lee et al., 2010
In the citing paper
“Like humans, it was found that aged wild type mice develop muscle insulin resistance, which was associated with increased muscle lipid (TAG/DAG) content (but no change in muscle ceramide content) and reduced muscle mitochondrial function.”
From Myosteatosis in the Context of Skeletal Muscle Function Deficit: An Interdisciplinary Workshop at the National Institute on Aging (2020) · cites this paper as Lee et al., 2010
In the citing paper
“Interestingly, all these effects of aging were abrogated in mice with targeted overexpression of catalase to the mitochondria.”
From Myosteatosis in the Context of Skeletal Muscle Function Deficit: An Interdisciplinary Workshop at the National Institute on Aging (2020) · cites this paper as Lee et al., 2010
In the citing paper
“there is substantial evidence showing increased ROS production and associated oxidative stress-induced damage to mitochondrial DNA (mtDNA) and ETC complexes in aged rodents and non-human primates (Figueiredo, Powers, Ferreira, Appell, and Duarte 2009;Lee, Choi, Birkenfeld, Alves, Jornayvaz, Jurczak, Zhang, Woo, Shadel, and Ladiges 2010;Lee, Wang, and Fanburg 1998;WANAGAT, CAO, PATHARE, and AIKEN 2”
From Successful aging: Advancing the science of physical independence in older adults (2015) · cites this paper as Lee et al. 2010
In the citing paper
“These same mice are also protected from mitochondrial dysfunction, decreased energy metabolism and lipid-induced insulin resistance in skeletal muscle (Lee et al., 2010).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Lee et al., 2010
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Citations
Cites
A RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATION
Bligh, E. G., & Dyer, W. J. (1959) · Canadian Journal of Biochemistry and Physiology · doi:10.1139/o59-099 · Cited by 54,751
Watterson, K. R., Bestow, D., Gallagher, J. R., Hamilton, D. L., Ashford, F. B., Meakin, P. J., & Ashford, M. L. J. (2012) · Neurosignals · doi:10.1159/000334144 · Cited by 3,395
Mitochondrial free radical generation, oxidative stress, and aging
Cadenas, E., & Davies, K. J. A. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00317-8 · Cited by 3,010
Cellular mechanisms of insulin resistance
Shulman, G. I. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10583 · Cited by 2,714
Self-citationHarris, M. I., Flegal, K. M., Cowie, C. C., Eberhardt, M. S., Goldstein, D. E., Little, R. R., Wiedmeyer, H.-M., & Byrd-Holt, D. D. (1998) · Diabetes Care · doi:10.2337/diacare.21.4.518 · Cited by 2,703
Reactive oxygen species have a causal role in multiple forms of insulin resistance
Houstis, N., Rosen, E. D., & Lander, E. S. (2006) · Nature · doi:10.1038/nature04634 · Cited by 2,525 · cited 3×
“…Stadtman, 2002; Wei et al., 1998), this remains a controversial topic (Anderson et al., 2009; Bashanet al., 2009;Bonnardetal., 2008;Evanset al., 2005;Houstis et al., 2006; Loh et al., 2009; Ristow et al., 2009), and in vivo studies assessing the potential role of oxidative stress in causing muscle…”
AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy
Hardie, D. G. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2249 · Cited by 2,261
Mitochondrial dysfunction in the elderly: possible role in insulin resistance
Petersen, K. F., Befroy, D., Dufour, S., Dziura, J., Ariyan, C., Rothman, D. L., DiPietro, L., Cline, G. W., & Shulman, G. I. (2003) · Science · doi:10.1126/science.1082889 · Cited by 2,107
Self-citationMitochondrial dysfunction and type 2 diabetes
Lowell, B. B., & Shulman, G. I. (2005) · Science · doi:10.1126/science.1104343 · Cited by 2,070
Self-citationOxidative damage and mitochondrial decay in aging.
Shigenaga, M. K., Hagen, T. M., & Ames, B. N. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.23.10771 · Cited by 2,055
Extension of murine life span by overexpression of catalase targeted to mitochondria
Schriner, S. E., Linford, N. J., Martin, G. M., Treuting, P., Ogburn, C. E., Emond, M., Coskun, P. E., Ladiges, W., Wolf, N., Van Remmen, H., et al. (2005) · Science · doi:10.1126/science.1106653 · Cited by 1,724
Self-citationAntioxidants prevent health-promoting effects of physical exercise in humans
Ristow, M., Zarse, K., Oberbach, A., Klöting, N., Birringer, M., Kiehntopf, M., Stumvoll, M., Kahn, C. R., & Blüher, M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903485106 · Cited by 1,582
Yu, C., Chen, Y., Cline, G. W., Zhang, D., Zong, H., Wang, Y., Bergeron, R., Kim, J. K., Cushman, S. W., Cooney, G. J., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200958200 · Cited by 1,561
Self-citationMechanism of hepatic insulin resistance in non-alcoholic fatty liver disease
Samuel, V. T., Liu, Z.-X., Qu, X., Elder, B. D., Bilz, S., Befroy, D., Romanelli, A. J., & Shulman, G. I. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313478200 · Cited by 1,322
Self-citationGriffin, M. E., Marcucci, M. J., Cline, G. W., Bell, K., Barucci, N., Lee, D., Goodyear, L. J., Kraegen, E. W., White, M. F., & Shulman, G. I. (1999) · Diabetes · doi:10.2337/diabetes.48.6.1270 · Cited by 1,267
Self-citationAnderson, E. J., Lustig, M. E., Boyle, K. E., Woodlief, T. L., Kane, D. A., Lin, C.-T., Price, J. W., Kang, L., Rabinovitch, P. S., Szeto, H. H., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37048 · Cited by 1,253
Self-citationZong, H., Ren, J. M., Young, L. H., Pypaert, M., Mu, J., Birnbaum, M. J., & Shulman, G. I. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.252625599 · Cited by 1,036
Morino, K., Petersen, K. F., & Shulman, G. I. (2006) · Diabetes · doi:10.2337/db06-s002 · Cited by 853
Self-citationBonnard, C., Durand, A., Peyrol, S., Chanseaume, E., Chauvin, M.-A., Morio, B., Vidal, H., & Rieusset, J. (2008) · Journal of Clinical Investigation · doi:10.1172/jci32601 · Cited by 819
Morino, K. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25151 · Cited by 811
UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals
Andrews, Z. B., Liu, Z.-W., Walllingford, N., Erion, D. M., Borok, E., Friedman, J. M., Tschöp, M. H., Shanabrough, M., Cline, G., Shulman, G. I., et al. (2008) · Nature · doi:10.1038/nature07181 · Cited by 710
Self-citationAlessi, D. R., Barry Caudwell, F., Andjelkovic, M., Hemmings, B. A., & Cohen, P. (1996) · FEBS Letters · doi:10.1016/s0014-5793(96)01370-1 · Cited by 628
The Molecular Basis for Oxidative Stress-Induced Insulin Resistance
Evans, J. L., Maddux, B. A., & Goldfine, I. D. (2005) · Antioxidants & Redox Signaling · doi:10.1089/ars.2005.7.1040 · Cited by 587
Reactive oxygen species enhance insulin sensitivity
Loh, K., Deng, H., Fukushima, A., Cai, X., Boivin, B., Galic, S., Bruce, C., Shields, B. J., Skiba, B., Ooms, L. M., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.08.009 · Cited by 581
Chronic activation of AMP kinase results in NRF-1 activation and mitochondrial biogenesis
Bergeron, R., Ren, J. M., Cadman, K. S., Moore, I. K., Perret, P., Pypaert, M., Young, L. H., Semenkovich, C. F., & Shulman, G. I. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.281.6.e1340 · Cited by 561
Self-citationAging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis
Reznick, R. M., Zong, H., Li, J., Morino, K., Moore, I. K., Yu, H. J., Liu, Z.-X., Dong, J., Mustard, K. J., Hawley, S. A., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.01.008 · Cited by 555
Self-citationPositive and Negative Regulation of Insulin Signaling by Reactive Oxygen and Nitrogen Species
Bashan, N., Kovsan, J., Kachko, I., Ovadia, H., & Rudich, A. (2009) · Physiological Reviews · doi:10.1152/physrev.00014.2008 · Cited by 542 · cited 1×
“The role of ROS in causing age-associated reduction in mitochondrial function is controversial (Bashan et al., 2009; Bonnard et al., 2008; Evans et al., 2005; Houstis et al., 2006; Loh et al., 2009; Ristow et al., 2009).”
Furda, A. M., Santos, J. H., Meyer, J. N., & Houten, B. V. (2014) · Methods in molecular biology · doi:10.1007/978-1-62703-739-6_31 · Cited by 387
Self-citationSantos, J. H., Meyer, J. N., Mandavilli, B. S., & Houten, B. V. (2008) · Methods in molecular biology · doi:10.1385/1-59259-973-7:183 · Cited by 289
Self-citationChoi, C. S., Befroy, D. E., Codella, R., Kim, S., Reznick, R. M., Hwang, Y.-J., Liu, Z.-X., Lee, H.-Y., Distefano, A., Samuel, V. T., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810339105 · Cited by 279
Self-citationWei, Y., Lu, C., Lee, H., Pang, C., & Ma, Y. (1998) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1998.tb09899.x · Cited by 265
Self-citationNeschen, S., Morino, K., Hammond, L. E., Zhang, D., Liu, Z.-X., Romanelli, A. J., Cline, G. W., Pongratz, R. L., Zhang, X.-M., Choi, C. S., et al. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.06.006 · Cited by 261
Self-citationOverexpression of Mn Superoxide Dismutase Does Not Increase Life Span in Mice
Jang, Y. C., Pérez, V., Song, W. J., Lustgarten, M. S., Salmon, A. B., Mele, J., Qi, W., Liu, Y., Liang, H., Chaudhuri, A. R., et al. (2009) · The Journals of Gerontology Series A · doi:10.1093/gerona/glp100 · Cited by 205
Choi, C. S., Fillmore, J. J., Kim, J. K., Liu, Z., Kim, S., Collier, E. F., Kulkarni, A. S., Distefano, A. G., Hwang, Y.-J., Kahn, M., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci13579 · Cited by 183
Self-citationSamuel, V. T., Choi, C. S., Phillips, T. G., Romanelli, A. J., Geisler, J. G., Bhanot, S., McKay, R. A., Monia, B. P., Shutter, J. R., Lindberg, R. A., et al. (2006) · Diabetes · doi:10.2337/db05-0705 · Cited by 177
Self-citationStadtman, E. R. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00904-8 · Cited by 133
Pérez, V. I., Lew, C. M., Cortez, L. A., Webb, C. R., Rodriguez, M. R., Liu, Y.-H., Qi, W., Li, Y., Chaudhuri, A., Remmen, H. V., et al. (2008) · Free Radical Biology & Medicine · doi:10.1016/j.freeradbiomed.2007.11.018 · Cited by 118
Zhang, D., Christianson, J., Liu, Z., Tian, L., Choi, C. S., Neschen, S., Dong, J., Wood, P. A., & Shulman, G. I. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.03.012 · Cited by 84
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Self-citationMechanisms and disease consequences of nonalcoholic fatty liver disease
Loomba, R., Friedman, S. L., & Shulman, G. I. (2021) · Cell · doi:10.1016/j.cell.2021.04.015 · Cited by 2,002
Self-citationChemistry and biology of reactive oxygen species in signaling or stress responses
Dickinson, B. C., & Chang, C. J. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.607 · Cited by 1,821
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Samuel, V. T., & Shulman, G. I. (2016) · Journal of Clinical Investigation · doi:10.1172/jci77812 · Cited by 1,484
Self-citationMitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype
Wiley, C. D., Velarde, M. C., Lecot, P., Liu, S., Sarnoski, E. A., Freund, A., Shirakawa, K., Lim, H. W., Davis, S. S., Ramanathan, A., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.11.011 · Cited by 1,275
“, muscle cells and neurons) (Herbst et al., 2007; Lee et al., 2010; Safdar et al., 2010; Wallace, 2010).”
Background
Metadata
- Authors
- Lee, H.-Y., Choi, C. S., Birkenfeld, A. L., Alves, T. C., Jornayvaz, F. R., Jurczak, M. J., Zhang, D., Woo, D. K., Shadel, G. S., Ladiges, W., Rabinovitch, P. S., Santos, J. H., Petersen, K. F., Samuel, V. T., & Shulman, G. I.
- Affiliations
- Howard Hughes Medical Institute (US)
- Gachon University (KR)
- Yale University (US)
- University of Washington (US)
- Rutgers New Jersey Medical School (US)
- Corresponding author
- Shulman, Gerald I.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 12
- Issue
- 6
- Pages
- 668-674
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC3013349
- OpenAlex
- W2056525347
- Cited by
- 319
- References
- 38
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 17 · 2023: 7 · 2022: 16 · 2021: 15 · 2020: 21 · 2019: 22 · 2018: 20 · 2017: 16 · 2016: 26 · 2015: 28 · 2014: 38 · 2013: 26 · 2012: 33
- FWCI
- 10.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 959 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- PubMed Central (acceptedVersion)
- Site cant be reached (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- U.S. Department of Veterans Affairs
- U.S. Public Health Service (P01 AG001751, P01 ES01116, R01 AG23686, R01 DK40936, U24 DK076169)
- Deutsche Forschungsgemeinschaft (Bi1292/2-1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- catalase, mitochondrial targeting, muscle aging, insulin resistance, mitochondrial function, oxidative damage, intramyocellular lipid, energy metabolism, AMPK, mitochondrial biogenesis, ATP production, free radicals
- MeSH terms
- Adenosine Triphosphate, Aging, Animals, Catalase, DNA Damage, Energy Metabolism, Humans, Insulin, Insulin Resistance, Male, Mice, Transgenic, Mitochondria, Oxygen Consumption, Reactive Oxygen Species, Oxidative Stress, Muscle, Skeletal, Microscopy, Electron, Transmission, Mice
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