The Mitochondrial Hsp90 TRAP1 and Alzheimer’s Disease
Alzheimer’s Disease (AD) is the most common form of dementia, characterised by intra- and extracellular protein aggregation. In AD, the cellular protein quality control (PQC) system is derailed and fails to prevent the formation of these aggregates. Especially the mitochondrial paralogue of the cons...
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| Format: | Article |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.697913/full |
| _version_ | 1818601065074917376 |
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| author | Françoise A. Dekker Françoise A. Dekker Françoise A. Dekker Stefan G. D. Rüdiger Stefan G. D. Rüdiger |
| author_facet | Françoise A. Dekker Françoise A. Dekker Françoise A. Dekker Stefan G. D. Rüdiger Stefan G. D. Rüdiger |
| author_sort | Françoise A. Dekker |
| collection | DOAJ |
| description | Alzheimer’s Disease (AD) is the most common form of dementia, characterised by intra- and extracellular protein aggregation. In AD, the cellular protein quality control (PQC) system is derailed and fails to prevent the formation of these aggregates. Especially the mitochondrial paralogue of the conserved Hsp90 chaperone class, tumour necrosis factor receptor-associated protein 1 (TRAP1), is strongly downregulated in AD, more than other major PQC factors. Here, we review molecular mechanism and cellular function of TRAP1 and subsequently discuss possible links to AD. TRAP1 is an interesting paradigm for the Hsp90 family, as it chaperones proteins with vital cellular function, despite not being regulated by any of the co-chaperones that drive its cytosolic paralogues. TRAP1 encloses late folding intermediates in a non-active state. Thereby, it is involved in the assembly of the electron transport chain, and it favours the switch from oxidative phosphorylation to glycolysis. Another key function is that it ensures mitochondrial integrity by regulating the mitochondrial pore opening through Cyclophilin D. While it is still unclear whether TRAP1 itself is a driver or a passenger in AD, it might be a guide to identify key factors initiating neurodegeneration. |
| first_indexed | 2024-12-16T12:45:27Z |
| format | Article |
| id | doaj.art-568cfcdb58bd43958ba0640481e44389 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-12-16T12:45:27Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-568cfcdb58bd43958ba0640481e443892022-12-21T22:31:19ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-06-01810.3389/fmolb.2021.697913697913The Mitochondrial Hsp90 TRAP1 and Alzheimer’s DiseaseFrançoise A. Dekker0Françoise A. Dekker1Françoise A. Dekker2Stefan G. D. Rüdiger3Stefan G. D. Rüdiger4Medicinal Chemistry, Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, Amsterdam, NetherlandsCellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, NetherlandsScience for Life, Utrecht University, Utrecht, NetherlandsCellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, NetherlandsScience for Life, Utrecht University, Utrecht, NetherlandsAlzheimer’s Disease (AD) is the most common form of dementia, characterised by intra- and extracellular protein aggregation. In AD, the cellular protein quality control (PQC) system is derailed and fails to prevent the formation of these aggregates. Especially the mitochondrial paralogue of the conserved Hsp90 chaperone class, tumour necrosis factor receptor-associated protein 1 (TRAP1), is strongly downregulated in AD, more than other major PQC factors. Here, we review molecular mechanism and cellular function of TRAP1 and subsequently discuss possible links to AD. TRAP1 is an interesting paradigm for the Hsp90 family, as it chaperones proteins with vital cellular function, despite not being regulated by any of the co-chaperones that drive its cytosolic paralogues. TRAP1 encloses late folding intermediates in a non-active state. Thereby, it is involved in the assembly of the electron transport chain, and it favours the switch from oxidative phosphorylation to glycolysis. Another key function is that it ensures mitochondrial integrity by regulating the mitochondrial pore opening through Cyclophilin D. While it is still unclear whether TRAP1 itself is a driver or a passenger in AD, it might be a guide to identify key factors initiating neurodegeneration.https://www.frontiersin.org/articles/10.3389/fmolb.2021.697913/fullprotein foldingproteostasismolecular chaperonesprotein quality controlprotein aggregationneurodegeneration |
| spellingShingle | Françoise A. Dekker Françoise A. Dekker Françoise A. Dekker Stefan G. D. Rüdiger Stefan G. D. Rüdiger The Mitochondrial Hsp90 TRAP1 and Alzheimer’s Disease Frontiers in Molecular Biosciences protein folding proteostasis molecular chaperones protein quality control protein aggregation neurodegeneration |
| title | The Mitochondrial Hsp90 TRAP1 and Alzheimer’s Disease |
| title_full | The Mitochondrial Hsp90 TRAP1 and Alzheimer’s Disease |
| title_fullStr | The Mitochondrial Hsp90 TRAP1 and Alzheimer’s Disease |
| title_full_unstemmed | The Mitochondrial Hsp90 TRAP1 and Alzheimer’s Disease |
| title_short | The Mitochondrial Hsp90 TRAP1 and Alzheimer’s Disease |
| title_sort | mitochondrial hsp90 trap1 and alzheimer s disease |
| topic | protein folding proteostasis molecular chaperones protein quality control protein aggregation neurodegeneration |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2021.697913/full |
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