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Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3
Open accessAbstract
The Hsc/Hsp70 co-chaperones of the BAG (Bcl-2-associated athanogene) protein family are modulators of protein quality control. We examined the specific roles of BAG1 and BAG3 in protein degradation during the aging process. We show that BAG1 and BAG3 regulate proteasomal and macroautophagic pathways, respectively, for the degradation of polyubiquitinated proteins. Moreover, using models of cellular aging, we find that a switch from BAG1 to BAG3 determines that aged cells use more intensively the macroautophagic system for turnover of polyubiquitinated proteins. This increased macroautophagic flux is regulated by BAG3 in concert with the ubiquitin-binding protein p62/SQSTM1. The BAG3/BAG1 ratio is also elevated in neurons during aging of the rodent brain, where, consistent with a higher macroautophagy activity, we find increased levels of the autophagosomal marker LC3-II as well as a higher cathepsin activity. We conclude that the BAG3-mediated recruitment of the macroautophagy pathway is an important adaptation of the protein quality control system to maintain protein homeostasis in the presence of an enhanced pro-oxidant and aggregation-prone milieu characteristic of aging.
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“Increasing data indicate a significant association between senescence and autophagy in various cell systems (Gerland et al. 2003; Gamerdinger et al. 2009; Sasaki et al. 2010; Capparelli et al. 2012; Dörr et al. 2013).”
From Cellular senescence and its effector programs (2014) · cites this paper as Gamerdinger et al. 2009
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“Gamerdinger et al. (2009) showed a gradual shift in the degradation pathway for polyubiquitinated proteins from the proteasome pathway to autophagy during replicative senescence in HDFs.”
From Cellular senescence and its effector programs (2014) · cites this paper as Gamerdinger et al. 2009
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“p62 interacts with BAG3, a HSC70–HSP70 co-chaperone, which mediates the recruitment of unfolded proteins to the macroautophagy pathway for protein quality control (Gamerdinger et al., 2009).”
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“Population data has shown that the early activation of autophagy, followed by its decrease, is accompanied by a concomitant increase of senescence, in agreement with other models of autophagy and senescence induction.(51,52) In single cells, however, autophagy can decrease before, after or concomitant with cell enlarg…”
ResultSeidel, K., Vinet, J., den Dunnen, W. F. A., Brunt, E. R. P., Meister, M., Boncoraglio, A., Zijlstra, M. P., Boddeke, H. W. G. M., Rüb, U., Kampinga, H. H., et al. (2011) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2011.01198.x · Cited by 101
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“Gamerdinger and colleagues [166] revealed that during aging BAG1 is downregulated, which results in a reduction of proteasome activity, and BAG3 is upregulated, which turns the switch on toward the macroautophagic degradation activity.”
BackgroundThe dialogue between the ubiquitin-proteasome system and autophagy: Implications in ageing
Sun‐Wang, J. L., Ivanova, S., & Antonio Zorzano, A. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101203 · Cited by 98
Amino acids and autophagy: cross-talk and co-operation to control cellular homeostasis
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Modulation of Amyloid States by Molecular ChaperonesPreprint
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“in concert with SQSTM1 to stimulate autophagy-lysosomal pathway [93].”
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BackgroundIdentification of the Drosophila Ortholog of HSPB8
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RAB3GAP1 and RAB3GAP2 modulate basal and rapamycin-induced autophagy
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“Immunoblotting, co-immunoprecipitation, and immunocytochemistry Immunoblot analyses were performed as described previously.(53) Generally, 15 mg of total protein were subjected to SDS–PAGE using precast NuPAGE 4–12% Bis-Tris gels (Invitrogen, NPO322) or hand-cast 12% Bis-Tris gels.”
MethodInfluentialSelf-citationInomata, M., Niida, S., Shibata, K., & Into, T. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0819-y · Cited by 94
“Sources of antibodies used are: anti-TRIF rabbit polyclonal antibody (Alexis; AL227), anti-BAG3 rabbit polyclonal antibody (Abcam; ab86298), antiBNIP3L (NIX) rabbit polyclonal antibody (Abcam; ab8399), anti-NDP52 (CALCOCO2) rabbit polyclonal antibody (Abcam; ab68588), anti-Flag M2 monoclonal antibody (Sigma-Aldrich; F…”
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Self-citationBAG3-mediated proteostasis at a glance
Klimek, C., Kathage, B., Wördehoff, J., & Höhfeld, J. (2017) · Journal of Cell Science · doi:10.1242/jcs.203679 · Cited by 91
“…BAG1/BAG3 ratio provides a switch between chaperone-assisted proteasomal and autophagic degradation Rauch and Gestwicki, 2014; Minoia et al., 2014; Gamerdinger et al., 2009; Sondermann et al., 2001; Lüders et al., 2000 BAG2 Competitive binding to the HSP70 ATPase domain, NEF, inhibits…”
BackgroundInfluentialNeuromuscular Diseases Due to Chaperone Mutations: A Review and Some New Results
Sarparanta, J., Jonson, P. H., Kawan, S., & Udd, B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041409 · Cited by 90
Connecting autophagy to senescence in pathophysiology
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Myopathy associated BAG3 mutations lead to protein aggregation by stalling Hsp70 networks
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“It has been reported that BAG3 promotes the turnover of aggregates via autophagy (Gamerdinger et al., 2009).”
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Cassidy, L. D., & Narita, M. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13269 · Cited by 93
Pathophysiology of protein aggregation and extended phenotyping in filaminopathy
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“Other chaperones determine whether misfolded or aggregated proteins are subsequently degraded by the ubiquitin–proteasome machinery or through the autophagy pathway (Massey et al., 2006; Arndt et al., 2007, 2010; Carra et al., 2008; Gamerdinger et al., 2009).”
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Chaperone mediated autophagy degrades TDP-43 protein and is affected by TDP-43 aggregation
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“Such susceptibility would also account for the accumulation of high-MW p62 observed in models of aging [77, 90].”
BackgroundTherapeutic targeting of BAG3: considering its complexity in cancer and heart disease
Kirk, J. A., Cheung, J. Y., & Feldman, A. M. (2021) · Journal of Clinical Investigation · doi:10.1172/jci149415 · Cited by 76
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“The value of autophagic flux was quantitatively evaluated according to previous reports by subtracting the LC3-II levels in mice without CQ treatment from the LC3-II levels in mice treated with CQ (25, 26).”
MethodMaintaining proteostasis under mechanical stress
Höhfeld, J., Benzing, T. R., Bloch, W., Fürst, D. O., Gehlert, S., Hesse, M., Hoffmann, B., Hoppe, T., Huesgen, P. F., Köhn, M., et al. (2021) · EMBO Reports · doi:10.15252/embr.202152507 · Cited by 77
“It triggers the recruitment of the autophagic ubiquitin adaptor SQSTM1/p62 to stimulate the engulfment of the BAG3 chaperone complex by autophagosome precursor membranes, so-called phagophores, leading to client degradation in autolysosomes (Fig 3B) (Gamerdinger et al , 2009; Arndt et al , 2010).”
Influence of Normal Aging on Brain Autophagy: A Complex Scenario
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“…the mechanism of action of the HSPB8–BAG3– HSC70 complex, it was found that BAG3 interacts with the macroautophagy receptor protein p62/SQSTM1 (Gamerdinger et al., 2009). p62 is a multi-adaptor protein that can bind simultaneously to ubiquitin and to the autophagosome membrane-associated…”
The BEACH-containing protein WDR81 coordinates p62 and LC3C to promote aggrephagy
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“Autophagy can selectively remove ubiquitinated and aggregated proteins, thus serving as a protein quality-control sys-tem (Rubinsztein, 2006; Gamerdinger et al., 2009).”
BackgroundAutophagy and MHC-restricted antigen presentation
Valečka, J., Almeida, C. R., Su, B., Pierre, P., & Gatti, E. (2018) · Molecular Immunology · doi:10.1016/j.molimm.2018.05.009 · Cited by 78
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“BAG3 and its interacting proteins (3, 9).”
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Self-citationInsights on Human Small Heat Shock Proteins and Their Alterations in Diseases
Tedesco, B., Cristofani, R., Ferrari, V., Cozzi, M., Rusmini, P., Casarotto, E., Chierichetti, M., Mina, F., Galbiati, M., Piccolella, M., et al. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.842149 · Cited by 76
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“Although BAG1 interacts with the proteasome and increases Hsp70 client protein degradation (35), BAG3 inhibits proteasomal degradation ofHsp70 clients (36) and participates in the recruitment for autophagy (37, 38).”
BackgroundAutophagic Pathways to Clear the Tau Aggregates in Alzheimer’s Disease
Gorantla, N. V., & Chinnathambi, S. (2020) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-020-00897-0 · Cited by 74
“This is resolved by the levels of BAG proteins where abundance of BAG1 would direct the client degradation by UPS and BAG3 degrades protein by autophagy (Gamerdinger et al. 2009; Stürner and Behl 2017).”
BackgroundChua, B. A., Lennan, C., Sunshine, M. J., Dreifke, D., Chawla, A., Bennett, E. J., & Signer, R. A. J. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.02.010 · Cited by 74
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“co-chaperone—mediates the degradation of damaged client proteins by a selective form of macroautophagy, thus maintaining cellular function by recruitment of the macroautophagy pathway (19).”
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“Consistent with the previously reported negative correlation of BAG1 and BAG3 expression in other cell types (Gamerdinger et al., 2009; Meng et al., 2014), BAG3 knockdown increased BAG1 expression in PDAC cells (Fig.”
ResultSuppression of astrocytic autophagy by αB-crystallin contributes to α-synuclein inclusion formation
Lu, S., Guo, Y.-S., Liang, P., Zhang, S., Yin, S., Yin, Y., Wang, X., Ding, F., Gu, X., & Zhou, J. (2019) · Translational Neurodegeneration · doi:10.1186/s40035-018-0143-7 · Cited by 74
Lessons from senescence: Chromatin maintenance in non-proliferating cells
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“BAG3 was recently described to be a molecular switch that determines whether proteins are degraded in a proteasomal or autophagic manner (Gamerdinger et al., 2009) and was found to increase autophagic activity (Carra, 2009).”
BackgroundHaidar, M., Asselbergh, B., Adriaenssens, E., Winter, V. D., Timmermans, J., Auer‐Grumbach, M., Juneja, M., & Timmerman, V. (2019) · Autophagy · doi:10.1080/15548627.2019.1569930 · Cited by 74
“A compensatory mechanism exists between autophagy and proteasomal degradation, which is mediated by a shift in the expression ratio of the BAG (BCL2 associated athanogene) family proteins BAG3 and BAG1 [27].”
BackgroundInfluentialKögel, D., Linder, B., Brunschweiger, A., Chines, S., & Behl, C. (2020) · Cells · doi:10.3390/cells9030574 · Cited by 72
Self-citationGuidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, J., Abeliovich, H., Acevedo‐Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Kölner Universitäts PublikationsServer (Universität zu Köln) · doi:10.5167/uzh-131237 · Cited by 69
Involvement of molecular chaperone in protein-misfolding brain diseases
Wankhede, N. L., Kale, M. B., Upaganlawar, A. B., Taksande, B. G., Umekar, M. J., Behl, T., Abdellatif, A. A. H., Bhaskaran, P. M., Dachani, S. R., Sehgal, A., et al. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.112647 · Cited by 73
Selective destruction of abnormal proteins by ubiquitin-mediated protein quality control degradation
Fredrickson, E. K., & Gardner, R. G. (2012) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2011.12.006 · Cited by 66
“BAG cochaperones vary in their CHIP-related function from negatively regulating CHIP-dependent ubiquitylation of Hsp70 client proteins (BAG-2 and BAG-5) [77, 78], to facilitating the interaction of CHIP-chaperone complexes with the proteasome (BAG-1) [79], or in helping recruit the protein p62 to the CHIP-chaperone co…”
BackgroundAutophagy and ageing: Insights from invertebrate model organisms
Lionaki, E., Markaki, M., & Tavernarakis, N. (2013) · Ageing Research Reviews · doi:10.1016/j.arr.2012.05.001 · Cited by 61
“More autophagic machinery components could also be involved (Gamerdinger et al., 2009).”
BackgroundWenger, T., Terawaki, S., Camosseto, V., Rassoul, R. A., Mies, A., Catalan, N., Cláudio, N., Clavarino, G., Gassart, A. D., Rigotti, F., et al. (2012) · Autophagy · doi:10.4161/auto.18806 · Cited by 72
Kathage, B., Gehlert, S., Ulbricht, A., Lüdecke, L., Tapia, V., Orfanos, Z., Wenzel, D., Bloch, W., Volkmer, R., Fleischmann, B. K., et al. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.10.007 · Cited by 68
The Role of Free Radicals in Autophagy Regulation: Implications for Ageing
Pajares, M. A., Cuadrado, A., Engedal, N., Jirsova, Z., & Cahová, M. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/2450748 · Cited by 69
BAG3 promotes autophagy and glutaminolysis via stabilizing glutaminase
Zhao, S. Q., Wang, J., Yan, J. Y., Zhang, D.-L., Liu, B.-Q., Jiang, J., Li, C. R., Li, S., Meng, X., & Wang, H. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1504-6 · Cited by 66
Molecular, functional, and pathological aspects of TDP-43 fragmentation
Chhangani, D., Martín‐Peña, A., & Rincón-Limas, D. E. (2021) · iScience · doi:10.1016/j.isci.2021.102459 · Cited by 65
“Since the ratio of BAG1/BAG3 determines the route of degradation for ubiquitinated proteins (Gamerdinger et al., 2009), the authors used BAG1 overexpression to degrade TDP-43 and its truncated forms through proteasome, while achieved their autophagic degradation through BAG3 overexpression.”
BackgroundCardiomyocyte autophagy: Remodeling, repairing, and reconstructing the heart
Cao, D. J., Gillette, T. G., & Hill, J. A. (2009) · Current Hypertension Reports · doi:10.1007/s11906-009-0070-1 · Cited by 69
Kaushik, S., & Cuervo, A. M. (2012) · Pharmacological Research · doi:10.1016/j.phrs.2012.10.002 · Cited by 66
Capano, L. S., Sato, C., Ficulle, E., Yu, A., Horie, K., Kwon, J.-S., Burbach, K. F., Barthélemy, N. R., Fox, S. G., Karch, C. M., et al. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2022.04.018 · Cited by 65
Differential autophagy power in the spinal cord and muscle of transgenic ALS mice
Crippa, V., Boncoraglio, A., Galbiati, M., Aggarwal, T., Rusmini, P., Giorgetti, E., Cristofani, R., Carra, S., Pennuto, M., & Poletti, A. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00234 · Cited by 63
“…in young tissues, paralleled by higher UPS activity, while BAG3 is expressed at higher levels in aged tissues, characterized by higher autophagic activity (Gamerdinger et al., 2009), and the BAG3:BAG1 ratio determines the fate of client proteins to be degraded through either UPS or autophagy.”
BackgroundBracher, A., & Verghese, J. (2014) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-319-11731-7_1 · Cited by 62
Activation of Autophagy Ameliorates Cardiomyopathy in Mybpc3 -Targeted Knockin Mice
Singh, S. R., Zech, A. T. L., Geertz, B., Reischmann, S., Osińska, H. E., Prondzynski, M., Krämer, E., Meng, Q., Redwood, C. S., van der Velden, J., et al. (2017) · Circulation Heart Failure · doi:10.1161/circheartfailure.117.004140 · Cited by 67
The lifecycle of skeletal muscle mitochondria in obesity
Pileggi, C. A., Parmar, G., & Harper, M. (2021) · Obesity Reviews · doi:10.1111/obr.13164 · Cited by 61
“cognate 71 (HSC70) to mediate delivery of targeted proteins to lysosomes (chaperone-mediated autophagy or CMA).(134,135) Autophagic responses can also contribute to cell death by offering a compartmentalized and controlled mechanism to remove cell components, through a pathway termed autophagy-dependent cell death (AD…”
BackgroundCellular senescence and protein degradation
Deschênes‐Simard, X., Lessard, F., Gaumont‐Leclerc, M., Bardeesy, N. M., & Ferbeyre, G. (2014) · Cell Cycle · doi:10.4161/cc.29335 · Cited by 66
A role of BAG3 in regulating SNCA/α-synuclein clearance via selective macroautophagy
Cao, Y.-L., Yang, Y., Mao, C., Zhang, X., Wang, C.-T., Yang, H. J., Lv, D.-J., Wang, F., Hu, L., & Liu, C. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.08.023 · Cited by 61
Dysregulated autophagy in restrictive cardiomyopathy due to Pro209Leu mutation in BAG3
Schänzer, A., Rupp, S., Gräf, S., Zengeler, D., Jux, C., Akintürk, H., Gulatz, L., Mazhari, N., Acker, T., Coster, R. V., et al. (2018) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2018.01.001 · Cited by 62
Zhang, L., Zhang, Z.-P., Zhang, X.-E., Lin, F.-S., & Ge, F. (2010) · Journal of Virology · doi:10.1128/jvi.00213-10 · Cited by 60
“These findings indicate that autophagosome formation and turnover may depend on BAG3 and BAG3 can stimulate autophagy processes (7, 8, 18).”
BackgroundKettern, N., Rogon, C., Limmer, A., Schild, H., & Höhfeld, J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016398 · Cited by 60
“to induce BAG-1 assisted degradation by the proteasome [17].”
BackgroundRadioresistant Cancer Cells Can Be Conditioned to Enter Senescence by mTOR Inhibition
Nam, H. Y., Han, M. W., Chang, H. W., Lee, Y. S., Lee, M., Lee, H. J., Lee, B. W., Lee, H. J., Lee, K. E., Jung, M. K., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-3516 · Cited by 65
“It is shown that autophagymediates the transition to a senescent phenotype by promoting highly efficient protein turnover and the translation of proteins necessary for senescence establishment (16, 30).”
Combination of Anti-Cancer Drugs with Molecular Chaperone Inhibitors
Shevtsov, M. A., Multhoff, G., Mikhaylova, E. R., Shibata, A., Guzhova, I. V., & Margulis, B. A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20215284 · Cited by 60
Tang, M., Ji, C., Pallo, S. P., Rahman, I., & Johnson, G. V. W. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.12.001 · Cited by 59
Fuchs, M., Luthold, C., Guilbert, S. M., Varlet, A., Lambert, H., Jetté, A., Elowe, S., Landry, J., & Lavoie, J. N. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005582 · Cited by 58
Tsuchiya, Y., Taniguchi, H., Ito, Y., Morita, T., Karim, M. R., Ohtake, N., Fukagai, K., Ito, T., Okamuro, S., Iemura, S., et al. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.01271-12 · Cited by 59
“These genes contribute to protein quality control and the activation of selective autophagy, another degradation pathway for ubiquitinated proteins (27, 28).”
BackgroundMcClung, J. M., McCord, T. J., RYAN, T. E., Schmidt, C. A., Green, T. D., Southerland, K. W., Reinardy, J. L., Mueller, S. B., Venkatraman, T. N., Lascola, C. D., et al. (2017) · Circulation · doi:10.1161/circulationaha.116.024873 · Cited by 56
Chaperone-assisted E3 ligase CHIP: A double agent in cancer
Kumar, S., Basu, M., & Ghosh, M. K. (2021) · Genes & Diseases · doi:10.1016/j.gendis.2021.08.003 · Cited by 59
“Due to this switching of degradation pathway from UPS to chaperone assisted selective autophagy (CASA) occur.(85,90) Furthermore, BAG2 is a co-chaperone which inhibits the E3 ligase activity of CHIP that promotes the client protein HSP72 refolding by reducing its ubiquitination.”
BackgroundAutophagy and ageing: implications for age-related neurodegenerative diseases
Carroll, B., Hewitt, G., & Korolchuk, V. I. (2013) · Essays in Biochemistry · doi:10.1042/bse0550119 · Cited by 60
“Specifi cally, an increase in the expression of the co-chaperone protein BAG3, at the expense of BAG1, has been observed during ageing representing a shift from UPS- to macroautophagy-dependent degradation [25].”
BackgroundMacromolecular Degradation Systems and Cardiovascular Aging
Nakayama, H., Nishida, K., & Otsu, K. (2016) · Circulation Research · doi:10.1161/circresaha.115.307495 · Cited by 56
“observed during replicative senescence in a human I90 cell model of aging.(121) A myriad of evidence indicates a strong association between senescence and autophagy in various cell types.”
BackgroundRusmini, P., Polanco, M. J., Cristofani, R., Cicardi, M. E., Meroni, M., Galbiati, M., Piccolella, M., Messi, E., Giorgetti, E., Lieberman, A. P., et al. (2015) · Scientific Reports · doi:10.1038/srep15174 · Cited by 56
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“Under conditions of proteasome insufficiency, BAG3 connects to aggregates of ubiquitinated proteins via the autophagic receptor– sequestosome protein p62/SQSTM1 (hereinafter called p62) (26).”
BackgroundThe Role of HSPB8, a Component of the Chaperone-Assisted Selective Autophagy Machinery, in Cancer
Cristofani, R., Piccolella, M., Crippa, V., Tedesco, B., Marelli, M. M., Poletti, A., & Moretti, R. M. (2021) · Cells · doi:10.3390/cells10020335 · Cited by 56
Identification of autophagy as a longevity-assurance mechanism in the aging modelPodospora anserina
Knuppertz, L., Hamann, A., Pampaloni, F., Stelzer, E. H. K., & Osiewacz, H. D. (2014) · Autophagy · doi:10.4161/auto.28148 · Cited by 57
“In contrast, in aged primary fibroblasts and in aged mouse brain, macroautophagy is increased.(109) The reasons for these seemingly contradictory findings are not clearly understood but may reflect species-, tissue- and cell type-specific differences in the age-related regulation of autophagy.”
BackgroundFLNC myofibrillar myopathy results from impaired autophagy and protein insufficiency
Ruparelia, A. A., Oorschot, V. M. J., Ramm, G., & Bryson‐Richardson, R. J. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw080 · Cited by 58
“Interestingly, it has been shown that in ageing cells there is a switch from BAG1 regulated proteasomal degradation of proteins to BAG3 mediated autophagic degradation of proteins (44).”
BackgroundWurmthaler, L. A., Sack, M., Gense, K., Hartig, J. S., & Gamerdinger, M. (2019) · Nature Communications · doi:10.1038/s41467-019-08412-w · Cited by 54
Self-citationChaperone-assisted proteostasis is essential for mechanotransduction in mammalian cells
Ulbricht, A., Arndt, V., & Höhfeld, J. (2013) · Communicative & Integrative Biology · doi:10.4161/cib.24925 · Cited by 53
Liebl, M. P., & Hoppe, T. (2016) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00074.2016 · Cited by 54
Metadata
- Authors
- Gamerdinger, M., Hajieva, P., Kaya, A. M., Wolfrum, U., Hartl, F. U., & Behl, C.
- Affiliations
- Johannes Gutenberg University Mainz (DE)
- Max Planck Institute of Biochemistry (DE)
- Corresponding author
- Behl, Christian
- Venue
- The EMBO Journal
- Published
- 2009-02-19
- Volume
- 28
- Issue
- 7
- Pages
- 889-901
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC2647772
- OpenAlex
- W2094186182
- Cited by
- 522
- References
- 42
- Citations by year
- 2026: 20 · 2025: 20 · 2024: 20 · 2023: 24 · 2022: 33 · 2021: 32 · 2020: 25 · 2019: 23 · 2018: 37 · 2017: 47 · 2016: 38 · 2015: 33 · 2014: 32 · 2013: 35 · 2012: 25
- FWCI
- 23.16
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- protein quality control, aging, BAG3, BAG-1, macroautophagy, autophagy, polyubiquitinated proteins, proteasome, p62, LC3-II, cathepsin activity, neuronal aging, brain aging, proteostasis, protein aggregation, oxidative stress
- MeSH terms
- Animals, Autophagy, DNA-Binding Proteins, Humans, Immunohistochemistry, Transcription Factors, Cellular Senescence, Rats, Sprague-Dawley, Microscopy, Electron, Transmission, Proteasome Endopeptidase Complex, Adaptor Proteins, Signal Transducing, Apoptosis Regulatory Proteins, Mice, Rats
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