118:-containing protein complex that mediates the fusion of autophagosome membrane precursors. The formed autophagosomes finally fuse with lysosomes, resulting in client degradation. There are 5 main components for the chaperone-assisted selective autophagy complex are the molecular chaperones, autophagy receptors, autophagy equipment, lysosomes, and the substrates. The damaged and misfolded proteins inside the cell are recognized by the molecular chaperones, which afterwards bind to them. The receptors attach themselves to substrates that are connected to chaperones. This helps the substrate degrade. The chaperone-assisted selective autophagy substrates could be sent to specific areas like aggresomes for additional processing. The aggresomes are stress-induced juxta-nuclear inclusion bodies that requires an intact microtubular network to colocalize misfolded proteins, molecular chaperones, and UPS components at the microtubule organizing center. The chaperone-assisted selective autophagy is dependent on the formation of a heteromeric complex. This consists of the heat shock proteins and BAG3. The BAG family has 6 cochaperone members and BAG1 was identified as an interactor of Bcl-2 proteins which is an anti-apoptotic protein. The activation of HSF1 is the primary mechanism by which heat shock, proteasome inhibition, oxidative stress, and other stressors increase BAG3 expression.
98:. The cochaperone BAG3 plays a vital role in maintaining homeostasis. BAG3 facilitates the cooperation of HSPA8 and HSPB8 during the recognition of nonnative client proteins. HSPBs are chaperones that interact with misfolded substrates without the need for ATP to avoid aggregation. HSPB8 interacts with other HSPBs weakly and mostly forms homodimers. STUB1 mediates the
53:
ligases. The ubiquitinated proteins are enclosed in autophagosomes, which eventually fuse with lysosomes, leading to the degradation of the dysfunctional proteins. Chaperone-assisted selective autophagy is a vital part of the cellular protein quality control system. It is essential for protein
145:. The adaptor simultaneously interacts with the ubiquitinated client and autophagosome membrane precursors, thereby inducing the autophagic engulfment of the client. Autophagosome formation during chaperone-assisted selective autophagy depends on an interaction of
106:. The adaptor simultaneously interacts with the ubiquitinated client and autophagosome membrane precursors, thereby inducing the autophagic engulfment of the client. Autophagosome formation during chaperone-assisted selective autophagy depends on an interaction of
173:. Furthermore, the expression of the cochaperone BAG3 is upregulated in aged neuronal cells, which correlates with an increased necessity to dispose oxidatively damaged proteins through autophagy. Chaperone-assisted selective autophagy is thus essential for
41:(Greek: ‘self-eating’) was initially identified as a catabolic process for the unselective degradation of cellular content in lysosomes under starvation conditions. However, autophagy also comprises selective degradation pathways, which depend on
192:. Mechanical tension results in unfolding of filamin, leading to recognition by the chaperone complex and to the autophagic degradation of damaged filamin. This is a prerequisite for the maintenance of the
157:-containing protein complex that mediates the fusion of autophagosome membrane precursors. The formed autophagosomes finally fuse with lysosomes, resulting in client degradation.
45:
conjugation to initiate sorting to lysosomes. In the case of chaperone-assisted selective autophagy, dysfunctional, nonnative proteins are recognized by molecular
196:
cytoskeleton in mechanically strained cells and tissues. Impairment of chaperone-assisted selective autophagy in patients and animal models causes
137:. BAG3 facilitates the cooperation of HSPA8 and HSPB8 during the recognition of nonnative client proteins. STUB1 mediates the
184:
In mechanically strained cells and tissues, chaperone-assisted selective autophagy mediates the degradation of the
737:"Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy"
165:
Proteins that are degraded by chaperone-assisted selective autophagy include pathogenic forms of the
344:"Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3"
170:
141:
of the chaperone-bound client, which induces the recruitment of the autophagic ubiquitin adaptor
102:
of the chaperone-bound client, which induces the recruitment of the autophagic ubiquitin adaptor
735:
Sarparanta J, Jonson PH, Golzio C, Sandell S, Luque H, Screen M, et al. (February 2012).
230:
Ulbricht A, Eppler FJ, Tapia VE, van der Ven PF, Hampe N, Hersch N, et al. (March 2013).
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488:"Development by self-digestion: molecular mechanisms and biological functions of autophagy"
301:
243:
8:
232:"Cellular mechanotransduction relies on tension-induced and chaperone-assisted autophagy"
46:
24:
614:
589:
398:"HspB8 and Bag3: a new chaperone complex targeting misfolded proteins to macroautophagy"
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Selcen D, Muntoni F, Burton BK, Pegoraro E, Sewry C, Bite AV, Engel AG (January 2009).
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Arndt V, Dick N, Tawo R, Dreiseidler M, Wenzel D, Hesse M, et al. (January 2010).
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The chaperone-assisted selective autophagy complex comprises the molecular chaperones
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The chaperone-assisted selective autophagy complex comprises the molecular chaperones
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Homma S, Iwasaki M, Shelton GD, Engvall E, Reed JC, Takayama S (September 2006).
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590:"The chaperone-assisted selective autophagy complex dynamics and dysfunctions"
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Gamerdinger M, Hajieva P, Kaya AM, Wolfrum U, Hartl FU, Behl C (April 2009).
290:"Chaperone-assisted selective autophagy is essential for muscle maintenance"
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639:"Mutation in BAG3 causes severe dominant childhood muscular dystrophy"
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688:"BAG3 deficiency results in fulminant myopathy and early lethality"
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Tedesco B, Vendredy L, Timmerman V, Poletti A (June 2023).
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and in mechanically strained cells and tissues such as
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Shaid S, Brandts CH, Serve H, Dikic I (January 2013).
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49:and become ubiquitinated by chaperone-associated
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437:Reggiori F, Klionsky DJ (February 2002).
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19:is a cellular process for the selective,
534:"Ubiquitination and selective autophagy"
153:, which triggers the cooperation with a
114:, which triggers the cooperation with a
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17:Chaperone-assisted selective autophagy
486:Levine B, Klionsky DJ (April 2004).
13:
439:"Autophagy in the eukaryotic cell"
14:
802:
692:The American Journal of Pathology
538:Cell Death and Differentiation
161:Clients and physiological role
1:
606:10.1080/15548627.2022.2160564
505:10.1016/S1534-5807(04)00099-1
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704:10.2353/ajpath.2006.060250
455:10.1128/EC.01.1.11-21.2002
23:-dependent degradation of
315:10.1016/j.cub.2009.11.022
257:10.1016/j.cub.2013.01.064
78:Components and mechanism
129:, and the cochaperones
90:, and the cochaperones
188:-crosslinking protein
360:10.1038/emboj.2009.29
169:protein, which cause
171:Huntington's disease
643:Annals of Neurology
550:10.1038/cdd.2012.72
306:2010CBio...20..143A
248:2013CBio...23..430U
492:Developmental Cell
655:10.1002/ana.21553
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64:skeletal muscle
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408:(2): 237–239.
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354:(7): 889–901.
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300:(2): 143–148.
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242:(5): 430–435.
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202:cardiomyopathy
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139:ubiquitination
100:ubiquitination
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54:homeostasis (
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791:Cell biology
747:(4): 450–5.
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175:proteostasis
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56:proteostasis
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208:References
167:Huntingtin
47:chaperones
594:Autophagy
402:Autophagy
51:ubiquitin
43:ubiquitin
39:Autophagy
33:lysosomes
25:chaperone
21:ubiquitin
785:Category
771:22366786
722:16936253
673:19085932
624:36594740
615:10262806
568:22722335
514:15068787
473:12455967
424:18094623
378:19229298
324:20060297
266:23434281
29:proteins
762:3315599
713:1698816
664:2639628
559:3524631
369:2647772
302:Bibcode
244:Bibcode
190:filamin
179:neurons
60:neurons
27:-bound
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151:SYNPO2
143:SQSTM1
112:SYNPO2
104:SQSTM1
194:actin
186:actin
155:VPS18
149:with
135:STUB1
127:HSPB8
123:HSPA8
116:VPS18
110:with
96:STUB1
88:HSPB8
84:HSPA8
68:heart
58:) in
767:PMID
718:PMID
669:PMID
620:PMID
564:PMID
510:PMID
469:PMID
420:PMID
374:PMID
320:PMID
262:PMID
200:and
147:BAG3
133:and
131:BAG3
125:and
108:BAG3
94:and
92:BAG3
86:and
72:lung
70:and
757:PMC
749:doi
708:PMC
700:doi
696:169
659:PMC
651:doi
610:PMC
602:doi
554:PMC
546:doi
500:doi
459:PMC
451:doi
410:doi
364:PMC
356:doi
310:doi
252:doi
177:in
31:in
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