Electron transfer between cytochrome c and p66Shc generates reactive oxygen species that trigger mitochondrial apoptosis
Open accessAbstract
Reactive oxygen species (ROS) are potent inducers of oxidative damage and have been implicated in the regulation of specific cellular functions, including apoptosis. Mitochondrial ROS increase markedly after proapoptotic signals, though the biological significance and the underlying molecular mechanisms remain undetermined. P66Shc is a genetic determinant of life span in mammals, which regulates ROS metabolism and apoptosis. We report here that p66Shc is a redox enzyme that generates mitochondrial ROS (hydrogen peroxide) as signaling molecules for apoptosis. For this function, p66Shc utilizes reducing equivalents of the mitochondrial electron transfer chain through the oxidation of cytochrome c. Redox-defective mutants of p66Shc are unable to induce mitochondrial ROS generation and swelling in vitro or to mediate mitochondrial apoptosis in vivo. These data demonstrate the existence of alternative redox reactions of the mitochondrial electron transfer chain, which evolved to generate proapoptotic ROS in response to specific stress signals.
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?
p66SHC sustains intracellular ROS and regulates redox signaling, mitochondrial apoptosis, and aging.
“P66SHC protein is the largest isoform encoded by the ShcA locus, typical of vertebrates, and it sustains intracellular levels of ROS (Giorgio et al., 2005 Gertz & Steegborn, 2010) and regulates redox signaling pathways (Frijhoff et al., 2014), mitochondrial apoptosis (Migliaccio et al., 2006), and aging (Trinei et al., 2009).”
From P66SHC deletion improves fertility and progeric phenotype of late-generation TERC-deficient mice but not their short lifespan (2016) · cites this paper as Giorgio et al., 2005
Within mitochondria, p66Shc increases oxidant production by oxidizing cytochrome c to produce hydrogen peroxide and activate the mitochondrial transition pore.
“Within the mitochondria, p66Shc increases oxidant production by oxidizing cytochrome c to produce hydrogen peroxide and activate the mitochondrial transition pore (153).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [153]
PKCβ-induced Ser26 phosphorylation of p66Shc triggers its transport from cytosol to mitochondria, where it promotes reactive oxygen species accumulation by oxidizing cytochrome c and leads to apoptosis.
“Induction of Ser26 phosphorylation of p66Shc by protein kinase C-β (PKCβ) triggers the transport of p66Shc from the cytosol to mitochondria, where it promotes ROS accumulation by oxidizing cytochrome c184, ultimately leading to apoptosis.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [184]
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
Biochemistry and molecular cell biology of diabetic complications
Brownlee, M. (2001) · Nature · doi:10.1038/414813a · Cited by 9,107 · see citing works
Hydroperoxide metabolism in mammalian organs.
Chance, B., Sies, H., & Boveris, A. (1979) · Physiological Reviews · doi:10.1152/physrev.1979.59.3.527 · Cited by 5,827 · see citing works
Danial, N. N., & Korsmeyer, S. J. (2004) · Cell · doi:10.1016/s0092-8674(04)00046-7 · Cited by 4,651 · see citing works
Mitochondria, Oxidants, and Aging
Balaban, R. S., Nemoto, S., & Finkel, T. (2005) · Cell · doi:10.1016/j.cell.2005.02.001 · Cited by 4,388 · see citing works
The Pathophysiology of Mitochondrial Cell Death
Green, D. R., & Kroemer, G. (2004) · Science · doi:10.1126/science.1099320 · Cited by 3,416 · see citing works
Mitochondrial diseases in man and mouse
Wallace, D. C. (1999) · Science · doi:10.1126/science.283.5407.1482 · Cited by 3,060 · see citing works
LeBel, C. P., Ischiropoulos, H., & Bondy, S. C. (1992) · Chemical Research in Toxicology · doi:10.1021/tx00026a012 · Cited by 2,694 · see citing works
The p66shc adaptor protein controls oxidative stress response and life span in mammals
Migliaccio, E., Giorgio, M., Mele, S., Pelicci, G., Reboldi, P., Pandolfi, P. P., Lanfrancone, L., & Pelicci, P. G. (1999) · Nature · doi:10.1038/46311 · Cited by 1,712 · see citing works
Self-citationA novel transforming protein (SHC) with an SH2 domain is implicated in mitogenic signal transduction
Pelicci, G., Lanfrancone, L., Grignani, F., McGlade, J. C., Cavallo, F., Forni, G., Nicoletti, I., Grignani, F., Pawson, T. J., & Pelicci, P. G. (1992) · Cell · doi:10.1016/0092-8674(92)90536-l · Cited by 1,326 · see citing works
Self-citationA Distinct Pathway Remodels Mitochondrial Cristae and Mobilizes Cytochrome c during Apoptosis
Scorrano, L., Ashiya, M., Buttle, K., Weiler, S., Oakes, S. A., Mannella, C. A., & Korsmeyer, S. J. (2002) · Developmental Cell · doi:10.1016/s1534-5807(01)00116-2 · Cited by 1,072 · see citing works
Redox Regulation of Forkhead Proteins Through a <i>p66shc</i> -Dependent Signaling Pathway
Nemoto, S., & Finkel, T. (2002) · Science · doi:10.1126/science.1069004 · Cited by 818 · see citing works
Zhao, H., Kalivendi, S., Zhang, H., Joseph, J., Nithipatikom, K., Vásquez-Vivar, J., & Kalyanaraman, B. (2003) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(03)00142-4 · Cited by 803 · see citing works
Cai, J., & Jones, D. P. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.19.11401 · Cited by 765 · see citing works
Mechanisms of cytochrome c release by proapoptotic BCL-2 family members
Scorrano, L., & Korsmeyer, S. J. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)00615-6 · Cited by 717 · see citing works
New concepts in reactive oxygen species and cardiovascular reperfusion physiology
Becker, L. C. (2003) · Cardiovascular Research · doi:10.1016/j.cardiores.2003.10.025 · Cited by 703 · see citing works
Petronilli, V., Costantini, P., Scorrano, L., Colonna, R., Passamonti, S., & Bernardi, P. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)89437-1 · Cited by 531 · see citing works
Self-citationSakon, S., Xue, X., Takekawa, M., Sasazuki, T., Okazaki, T., Kojima, Y., Piao, J., Yagita, H., Okumura, K., Doi, T., et al. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg379 · Cited by 497 · see citing works
Griparić, L., van der Wel, N. N., Orozco, I. J., Peters, P. J., & van der Bliek, A. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m400920200 · Cited by 468 · see citing works
Trinei, M., Giorgio, M., Cicalese, A., Barozzi, S., Ventura, A., Migliaccio, E., Milia, E., Padura, I. M., Raker, V. A., Maccarana, M., et al. (2002) · Oncogene · doi:10.1038/sj.onc.1205513 · Cited by 436 · see citing works
Self-citationA mitochondrial perspective on cell death
Bernardi, P., Petronilli, V., Lisa, F. D., & Forte, M. A. (2001) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)01745-x · Cited by 416 · see citing works
Self-citationMigliaccio, E., Mele, S., Salcini, A. E., Pelicci, G., Lai, K. V., Superti‐Furga, G., Pawson, T. J., Fiore, P. P. D., Lanfrancone, L., & Pelicci, P. G. (1997) · The EMBO Journal · doi:10.1093/emboj/16.4.706 · Cited by 395 · see citing works
Self-citationNapoli, C., Martin-Padura, I., de Nigris, F., Giorgio, M., Mansueto, G., Somma, P., Condorelli, M., Sica, G., De Rosa, G., & Pelicci, P. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0336359100 · Cited by 380 · see citing works
Self-citationMayer, M., & Noble, M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.16.7496 · Cited by 371 · see citing works
Deletion of p66 <sup>shc</sup> Gene Protects Against Age-Related Endothelial Dysfunction
Francia, P., delli Gatti, C., Bachschmid, M., Martin-Padura, I., Savoia, C., Migliaccio, E., Pelicci, P. G., Schiavoni, M., Lüscher, T. F., Volpe, M., et al. (2004) · Circulation · doi:10.1161/01.cir.0000147731.24444.4d · Cited by 298 · cited 3× · see citing works
“…et al., 1999; Trinei et al., 2002). t Intracellular ROS levels are decreased in p66Shc−/− m cells, as revealed by the reduced oxidation of ROS-senc sitive probes and the reduced accumulation of endogeR nous markers of oxidative stress (8-oxo-guanosine) i(Trinei et al., 2002; Francia et al., 2004).”
Self-citationOrsini, F., Migliaccio, E., Moroni, M., Contursi, C., Raker, V. A., Piccini, D., Martín-Padura, I., Pelliccia, G., Trinei, M., Bono, M., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m401844200 · Cited by 293 · see citing works
Self-citationCytochrome c as an electron shuttle between the outer and inner mitochondrial membranes.
Bernardi, P., & AZZONE, G. F. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)68946-5 · Cited by 201 · see citing works
Self-citationChen, X., Ferrigno, R., Yang, J., et al. (2002) · Langmuir · doi:10.1021/la0204794 · Cited by 186 · see citing works
p66SHC Promotes Apoptosis and Antagonizes Mitogenic Signaling in T Cells
Pacini, S., Pellegrini, M., Migliaccio, E., Patrussi, L., Ulivieri, C., Ventura, A., Carraro, F., Naldini, A., Lanfrancone, L., Pelicci, P. G., et al. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.4.1747-1757.2004 · Cited by 137 · see citing works
Self-citationp66 ShcA Modulates Tissue Response to Hindlimb Ischemia
Zaccagnini, G., Martelli, F., Fasanaro, P., Magenta, A., Gaetano, C., Carlo, A. D., Biglioli, P., Giorgio, M., Martín-Padura, I., Pelicci, P. G., et al. (2004) · Circulation · doi:10.1161/01.cir.0000129309.58874.0f · Cited by 110 · see citing works
Self-citationArmstrong, F. A. (2002) · Journal of the Chemical Society Dalton Transactions · doi:10.1039/b108359g · Cited by 107 · see citing works
Definition of the Interaction Domain for Cytochrome con Cytochrome c Oxidase
Zhen, Y., Hoganson, C. W., Babcock, Ǵ., & Ferguson-Miller, S. M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.53.38032 · Cited by 99 · see citing works
Callegari, A., Cosnier, S., Marcaccio, M., et al. (2004) · Journal of Materials Chemistry · doi:10.1039/b316806a · Cited by 90 · see citing works
Self-citationDo tumor-suppressive mechanisms contribute to organism aging by inducing stem cell senescence?
Pelicci, P. G. (2004) · Journal of Clinical Investigation · doi:10.1172/jci20750 · Cited by 85 · see citing works
Self-citationA Cryptic Targeting Signal Induces Isoform-specific Localization of p46Shc to Mitochondria
Ventura, A., Maccarana, M., Raker, V. A., & Pelicci, P. G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m307655200 · Cited by 60 · see citing works
Self-citationNitric Oxide and Mitochondrial Complex IV
Sarti, P., Arese, M., Bacchi, A., Barone, M. C., Forte, E., Mastronicola, D., Brunori, M., & Giuffrè, A. (2003) · IUBMB Life · doi:10.1080/15216540310001628726 · Cited by 56 · see citing works
Diwan, J. J., Yune, H. H., Bawa, R., et al. (1988) · Biochemical Pharmacology · doi:10.1016/0006-2952(88)90188-8 · Cited by 12 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Armstrong, F.A. (2002). Insights from protein film voltammetry into mechanisms of complex biological electron-transfer reactions. J. Chem. Soc., Dalton Trans. 5 , 661.
Cited by
Sorted by citations
How mitochondria produce reactive oxygen species
Murphy, M. P. (2009) · Biochemical Journal · doi:10.1042/bj20081386 · Cited by 8,207 · see citing works
Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?
Trachootham, D., Alexandre, J., & Huang, P. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2803 · Cited by 5,452 · see citing works
Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release
Zorov, D. B., Juhaszova, M., & Sollott, S. J. (2014) · Physiological Reviews · doi:10.1152/physrev.00026.2013 · Cited by 5,383 · see citing works
Oxyl radicals, redox-sensitive signalling cascades and antioxidants
Genestra, M. (2007) · Cellular Signalling · doi:10.1016/j.cellsig.2007.04.009 · Cited by 4,930 · see citing works
Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling
Ray, P. D., Huang, B.-W., & Tsuji, Y. (2012) · Cellular Signalling · doi:10.1016/j.cellsig.2012.01.008 · Cited by 4,373 · see citing works
Mitochondrial membrane permeabilization in cell death
Kroemer, G., Galluzzi, L., & Brenner, C. (2007) · Physiological Reviews · doi:10.1152/physrev.00013.2006 · Cited by 3,598 · see citing works
Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases
Phaniendra, A., Jestadi, D. B., & Periyasamy, L. (2015) · Indian Journal of Clinical Biochemistry · doi:10.1007/s12291-014-0446-0 · Cited by 2,886 · see citing works
Signal transduction by reactive oxygen species
Finkel, T. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201102095 · Cited by 2,322 · see citing works
Reactive Oxygen Species in Metabolic and Inflammatory Signaling
Forrester, S. J., Kikuchi, D. S., Hernandes, M. S., Xu, Q., & Griendling, K. K. (2018) · Circulation Research · doi:10.1161/circresaha.117.311401 · Cited by 2,081 · see citing works
Chemistry 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 · see citing works
Redox regulation of cell survival
Trachootham, D., Lu, W., Ogasawara, M. A., Valle, N. R.-D., & Huang, P. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1957 · Cited by 1,781 · see citing works
Oxidative stress and cancer: Have we moved forward?
Halliwell, B. (2007) · Biochemical Journal · doi:10.1042/bj20061131 · Cited by 1,302 · see citing works
Targeting Antioxidants to Mitochondria by Conjugation to Lipophilic Cations
Murphy, M. P., & Smith, R. A. J. (2007) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.47.120505.105110 · Cited by 1,173 · see citing works
Brand, M. D. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.04.001 · Cited by 1,063 · see citing works
Mitochondrial and metabolic dysfunction in ageing and age-related diseases
Amorim, J. A., Coppotelli, G., Rolo, A. P., Palmeira, C. M., Ross, J. M., & Sinclair, D. A. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00626-7 · Cited by 990 · see citing works
ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells
Snezhkina, A. V., Kudryavtseva, A. V., Kardymon, O. L., Savvateeva, M. V., Melnikova, N. V., Krasnov, G. S., & Dmitriev, A. A. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/6175804 · Cited by 934 · see citing works
Kregel, K. C., & Zhang, H. J. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00327.2006 · Cited by 883 · see citing works
The mitochondrial permeability transition from<i>in vitro</i>artifact to disease target
Bernardi, P., Krauskopf, A., Basso, E., Petronilli, V., Blalchy‐Dyson, E., Di Lisa, F., & Forte, M. A. (2006) · The FEBS Journal · doi:10.1111/j.1742-4658.2006.05213.x · Cited by 627 · see citing works
Self-citationRedox regulation of mitochondrial function
Handy, D. E., & Loscalzo, J. (2012) · Antioxidants & Redox Signaling · doi:10.1089/ars.2011.4123 · Cited by 588 · see citing works
Bell, E. L., Klimova, T. A., Eisenbart, J., Moraes, C. T., Murphy, M. P., Budinger, G. R. S., & Chandel, N. S. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200609074 · Cited by 568 · see citing works
Mitochondria and Endothelial Function
Kluge, M. A., Fetterman, J. L., & Vita, J. A. (2013) · Circulation Research · doi:10.1161/circresaha.111.300233 · Cited by 508 · see citing works
The Power of Plasticity—Metabolic Regulation of Hepatic Stellate Cells
Trivedi, P., Wang, S., & Friedman, S. L. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2020.10.026 · Cited by 427 · see citing works
Mitochondria and ageing: Role in heart, skeletal muscle and adipose tissue
Boengler, K., Kosiol, M., Mayr, M., Schulz, R., & Rohrbach, S. (2017) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12178 · Cited by 421 · see citing works
Bubici, C., Papa, S., Dean, K., & Franzoso, G. (2006) · Oncogene · doi:10.1038/sj.onc.1209936 · Cited by 399 · see citing works
Thomas, S. R., Witting, P. K., & Drummond, G. R. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2008.2027 · Cited by 383 · see citing works
Rota, M., LeCapitaine, N., Hosoda, T., Boni, A., De Angelis, A., Padin-Iruegas, M. E., Esposito, G., Vitale, S., Urbanek, K., Casarsa, C., et al. (2006) · Circulation Research · doi:10.1161/01.res.0000231289.63468.08 · Cited by 330 · see citing works
Self-citationIncreased longevity and refractoriness to Ca2+-dependent neurodegeneration in Surf1 knockout mice
Dell'Agnello, C., Leo, S., Agostino, A., Szabadkai, G., Tiveron, C., Zulian, A., Prelle, A., Roubertoux, P., Rizzuto, R., & Zeviani, M. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddl477 · Cited by 308 · see citing works
Self-citationSkeletal muscle insulin resistance: role of mitochondria and other ROS sources
Di Meo, S., Iossa, S., & Venditti, P. (2017) · Journal of Endocrinology · doi:10.1530/joe-16-0598 · Cited by 282 · see citing works
Kim, Y.-M., Kim, S.-J., Tatsunami, R., Yamamura, H., Fukai, T., & Ushio-Fukai, M. (2017) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00346.2016 · Cited by 251 · see citing works
Camici, G. G., Schiavoni, M., Francia, P., Bachschmid, M., Martin-Padura, I., Hersberger, M., Tanner, F. C., Pelicci, P., Volpe, M., Anversa, P., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0609656104 · Cited by 249 · see citing works
Self-citationThe role of mitochondrial dysfunction in age-related diseases
Lane, R. K., Hilsabeck, T., & Rea, S. L. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.05.021 · Cited by 205 · see citing works
Reduction in glutathione peroxidase 4 increases life span through increased sensitivity to apoptosis
Ran, Q., Liang, H., Ikeno, Y., Qi, W., Prolla, T. A., Roberts, L. J., Wolf, N., VanRemmen, H., & Richardson, A. (2007) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/62.9.932 · Cited by 195 · see citing works
Waypa, G. B., Guzy, R., Mungai, P. T., Mack, M. M., Marks, J. D., Roe, M. W., & Schumacker, P. T. (2006) · Circulation Research · doi:10.1161/01.res.0000247068.75808.3f · Cited by 191 · see citing works
Cancer and ageing: convergent and divergent mechanisms
Serrano, M., & Blasco, M. A. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2242 · Cited by 182 · see citing works
Bayir, H., Fadeel, B., Palladino, M. J., Witasp, E., Kurnikov, I. V., Tyurina, Y. Y., Tyurin, V. A., Amoscato, A. A., Jiang, J., Kochanek, P. M., et al. (2006) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2006.03.002 · Cited by 175 · see citing works
Senescence in Post-Mitotic Cells: A Driver of Aging?
von Zglinicki, T., Wan, T., & Miwa, S. (2021) · Antioxidants & Redox Signaling · doi:10.1089/ars.2020.8048 · Cited by 170 · see citing works
p66Shc-generated Oxidative Signal Promotes Fat Accumulation
Berniakovich, I., Trinei, M., Stendardo, M., Migliaccio, E., Minucci, S., Bernardi, P., Pelicci, P. G., & Giorgio, M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m804362200 · Cited by 161 · see citing works
Self-citationMitochondrial damage-associated molecular patterns and vascular function
Wenceslau, C. F., McCarthy, C. G., Szasz, T., Spitler, K., Goulopoulou, S., Webb, R. C., & Working Group on DAMPs in Cardiovascular Disease (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu047 · Cited by 135 · see citing works
Apoptosis and Aging: Role of p66 <sup>Shc</sup> Redox Protein
Migliaccio, E., Giorgio, M., & Pelicci, P. G. (2006) · Antioxidants & Redox Signaling · doi:10.1089/ars.2006.8.600 · Cited by 123 · see citing works
Self-citationSun, L., Xiao, L., Nie, J., Liu, F.-Y., Ling, G.-H., Zhu, X.-J., Tang, W.-B., Chen, W.-C., Xia, Y.-C., Zhan, M., et al. (2010) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00414.2010 · Cited by 114 · see citing works
Fadini, G. P., Ceolotto, G., Pagnin, E., de Kreutzenberg, S., & Avogaro, A. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2010.00642.x · Cited by 97 · see citing works
Berry, A., Capone, F., Giorgio, M., Pelicci, P. G., de Kloet, E. R., Alleva, E., Minghetti, L., & Cirulli, F. (2007) · Experimental Gerontology · doi:10.1016/j.exger.2006.05.018 · Cited by 81 · see citing works
Self-citationMontfort, C. V., Matias, N., Fernandez, A., Fucho, R., de la Rosa, L. C., Martinez-Chantar, M. L., Mato, J. M., Machida, K., Tsukamoto, H., Murphy, M. P., et al. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.05.024 · Cited by 83 · see citing works
van Hameren, G., Campbell, G., Deck, M., Berthelot, J., Gautier, B., Quintana, P., Chrast, R., & Tricaud, N. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0740-4 · Cited by 83 · see citing works
The Impact of Oxidative Stress on the Bone System in Response to the Space Special Environment
Tian, Y., Ma, X., Yang, C., Su, P., Yin, C., & Qian, A.-R. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18102132 · Cited by 80 · see citing works
Epigenetic Signatures and Vascular Risk in Type 2 Diabetes: A Clinical Perspective
Paneni, F., Costantino, S., Volpe, M., Lüscher, T. F., & Cosentino, F. (2013) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2013.07.003 · Cited by 70 · see citing works
Nuclear-encoded mitochondrial proteins and their role in cardioprotection
Boengler, K., Heusch, G., & Schulz, R. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.01.009 · Cited by 68 · see citing works
The Shc locus regulates insulin signaling and adiposity in mammals
Tomilov, A. A., Ramsey, J. J., Hagopian, K., Giorgio, M., Kim, K. M., Lam, A., Migliaccio, E., Lloyd, K. C., Berniakovich, I., Prolla, T. A., et al. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2010.00641.x · Cited by 64 · see citing works
“…ShcP knockout mice resist oxidative stress (Migliaccio et al., 1999) and that the longevity of ShcP mice has been attributed to oxidative stress resistance and changes in mitochondrial biogenesis (Trinei et al., 2009) and the role of p66Shc in mitochondrial apoptosis process (Giorgio et al., 2005).”
BackgroundSelf-citationMenini, S., Iacobini, C., Ricci, C., Oddi, G., Pesce, C., Pugliese, F., Block, K., Abboud, H. E., Giorgio, M., Migliaccio, E., et al. (2007) · Diabetologia · doi:10.1007/s00125-007-0728-7 · Cited by 64 · see citing works
Self-citationPhosphorylation of Cytochrome c Threonine 28 Regulates Electron Transport Chain Activity in Kidney
Mahapatra, G., Varughese, A., Ji, Q., Lee, I., Liu, J., Vaishnav, A., Sinkler, C., Kapralov, A. A., Moraes, C. T., Sanderson, T. H., et al. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.744664 · Cited by 61 · see citing works
Actions of 17β-estradiol and testosterone in the mitochondria and their implications in aging
Vasconsuelo, A., Milanesi, L., & Boland, R. (2013) · Ageing Research Reviews · doi:10.1016/j.arr.2013.09.001 · Cited by 55 · see citing works
Franzeck, F. C., Hof, D., Spescha, R. D., Hasun, M., Akhmedov, A., Steffel, J., Shi, Y., Cosentino, F., Tanner, F. C., von Eckardstein, A., et al. (2012) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2011.10.035 · Cited by 54 · see citing works
Martin-Padura, I., de Nigris, F., Migliaccio, E., Mansueto, G., Minardi, S., Rienzo, M., Lerman, L. O., Stendardo, M., Giorgio, M., De Rosa, G., et al. (2008) · Endothelium · doi:10.1080/10623320802487791 · Cited by 52 · see citing works
Self-citationThe P66Shc/mitochondrial permeability transition pore pathway determines neurodegeneration
Savino, C., Pelicci, P., & Giorgio, M. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/719407 · Cited by 46 · see citing works
Self-citationFrijhoff, J., Dagnell, M., Augsten, M., Beltrami, E., Giorgio, M., & Östman, A. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.12.022 · Cited by 43 · see citing works
Self-citationShahzad, K., Gadi, I., Nazir, S., Al-Dabet, M. M., Kohli, S., Bock, F., Breitenstein, L., Ranjan, S., Fuchs, T., Halloul, Z., et al. (2018) · Communications Biology · doi:10.1038/s42003-018-0108-5 · Cited by 40 · see citing works
Self-citationp66Shc-induced redox changes drive endothelial insulin resistance
Paneni, F., Costantino, S., & Cosentino, F. (2014) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2014.07.027 · Cited by 38 · see citing works
Zoccarato, F., Cavallini, L., & Alexandre, A. (2009) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-009-9238-2 · Cited by 31 · see citing works
p66Shc aging protein in control of fibroblasts cell fate
Suski, J. M., Karkucinska-Wieckowska, A., Lebiedzinska, M., Giorgi, C., Szczepanowska, J., Szabadkai, G., Duszynski, J., Pronicki, M., Pinton, P., & Wieckowski, M. R. (2011) · International Journal of Molecular Sciences · doi:10.3390/ijms12085373 · Cited by 22 · see citing works
Self-citationModelling the p53/p66Shc Aging Pathway in the Shortest Living Vertebrate Nothobranchius Furzeri
Priami, C., De Michele, G., Cotelli, F., Cellerino, A., Giorgio, M., Pelicci, P. G., & Migliaccio, E. (2015) · Aging and Disease · doi:10.14336/ad.2014.0228 · Cited by 16 · see citing works
Self-citationGiorgio, M., Stendardo, M., Migliaccio, E., & Pelicci, P. G. (2016) · Aging Cell · doi:10.1111/acel.12448 · Cited by 11 · see citing works
“P66SHC protein is the largest isoform encoded by the ShcA locus, typical of vertebrates, and it sustains intracellular levels of ROS (Giorgio et al., 2005 Gertz & Steegborn, 2010) and regulates redox signaling pathways (Frijhoff et al., 2014), mitochondrial apoptosis (Migliaccio et al., 2006), and aging (Trinei et al.…”
BackgroundInfluentialSelf-citation
- Authors
- Giorgio, M., Migliaccio, E., Orsini, F., Paolucci, D., Moroni, M., Contursi, C., Pelliccia, G., Luzi, L., Minucci, S., Marcaccio, M., Pinton, P., Rizzuto, R., Bernardi, P., Paolucci, F., & Pelicci, P. G.
- Affiliations
- IFOM (IT)
- University of Bologna (IT)
- European Institute of Oncology (IT)
- University of Ferrara (IT)
- University of Padua (IT)
- University of Milan (IT)
- Corresponding author
- Giorgio, Marco
- Pelicci, Pier Giuseppe
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2005-07
- Volume
- 122
- Issue
- 2
- Pages
- 221-233
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2150381945
- Cited by
- 1,176
- References
- 36
- Citations by year
- 2026: 26 · 2025: 45 · 2024: 41 · 2023: 42 · 2022: 52 · 2021: 56 · 2020: 71 · 2019: 64 · 2018: 56 · 2017: 56 · 2016: 56 · 2015: 55 · 2014: 83 · 2013: 66 · 2012: 72
- FWCI
- 18.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion, other-oa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- p66Shc, cytochrome c, electron transfer, reactive oxygen species, mitochondrial apoptosis, hydrogen peroxide, mitochondrial electron transport chain, redox signaling, oxidative stress, mitochondrial swelling, lifespan
- MeSH terms
- Src Homology 2 Domain-Containing, Transforming Protein 1, Amino Acid Sequence, Animals, Cells, Cultured, Electron Transport, Hydrogen Peroxide, Intracellular Membranes, Mitochondria, Liver, Molecular Sequence Data, Mutation, Oxidation-Reduction, Permeability, Signal Transduction, Apoptosis, Reactive Oxygen Species, Protein Structure, Tertiary, Cytochromes c, Adaptor Proteins, Signal Transducing, Mice, Shc Signaling Adaptor Proteins
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
