Cellular functional study of high molecular weight oligomers of mortaline and the ...
| Full text | |
| Author(s): |
Kiraly, Vanessa T. R.
[1]
;
Dores-Silva, Paulo R.
[1, 2]
;
Serrao, Vitor H. B.
[3]
;
Cauvi, David M.
[2]
;
De Maio, Antonio
[2, 4, 5]
;
Borges, Julio C.
[1]
Total Authors: 6
|
| Affiliation: | [1] Univ Sao Paulo, Sao Carlos Inst Chem, Sao Carlos, SP - Brazil
[2] Univ Calif, Sch Med, Dept Surg, La Jolla, CA - USA
[3] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON - Canada
[4] Univ Calif San Diego, Ctr Invest Hlth & Educ Dispar, La Jolla, CA 92093 - USA
[5] Univ Calif, Sch Med, Dept Neurosci, La Jolla, CA - USA
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | International Journal of Biological Macromolecules; v. 146, p. 320-331, MAR 1 2020. |
| Web of Science Citations: | 0 |
| Abstract | |
The Hsp70 family of heat shock proteins plays a critical function in maintaining cellular homeostasis within various subcellular compartments. The human mitochondrial Hsp70 (HSPA9) has been associated with cellular death, senescence, cancer and neurodegenerative diseases, which is the rational for the name mortalin. It is well documented that mortalin, such as other Hsp70s, is prone to self-aggregation, which is related to mitochondria biogenesis failure. Here, we investigated the assembly, structure and function of thermic aggregates/oligomers of recombinant human mortalin and Hsp70-1A (HSPA1A). Summarily, both Hsp70 thermic aggregates have characteristics of supramolecular assemblies. They display characteristic organized structures and partial ATPase activity, despite their nanometric size. Indeed, we observed that the interaction of these aggregates/oligomers with liposomes is similar to monomeric Hsp70s and, finally, they were non-toxic over neuroblastoma cells. These findings revealed that high molecular mass oligomers of mortalin and Hsp70-1A preserved some of the fundamental functions of these proteins. (C) 2019 Elsevier B.V. All rights reserved. (AU) | |
| FAPESP's process: | 17/26131-5 - The chaperome: study of the relationship of the structure of its components and the maintenance of proteostasis |
| Grantee: | Carlos Henrique Inacio Ramos |
| Support type: | Research Projects - Thematic Grants |
| FAPESP's process: | 14/07206-6 - Studies of the mitochondrial HSP70 of human and protozoa: structural and functional approaches |
| Grantee: | Julio Cesar Borges |
| Support type: | Regular Research Grants |
| FAPESP's process: | 11/23110-0 - Using isothermal titration calorimetry for the determination of thermodynamic properties of protein-ligand and protein-protein interactions |
| Grantee: | Julio Cesar Borges |
| Support type: | Regular Research Grants |
| FAPESP's process: | 12/50161-8 - Study of the structure and function of the Hsp90 chaperone with emphasis on its role in cellular homeostasis |
| Grantee: | Carlos Henrique Inacio Ramos |
| Support type: | Research Projects - Thematic Grants |
| FAPESP's process: | 17/07335-9 - Studies of human HSP70 isoforms residing in the cytoplasm and mitochondria and their high molecular weight oligomers: interaction with co-chaperones and client proteins |
| Grantee: | Julio Cesar Borges |
| Support type: | Regular Research Grants |
| FAPESP's process: | 14/16646-0 - Human mortalin: interaction with co-chaperones, p53 and mutants, aggregation kinectics, regulation/modulation and vesicle secretion |
| Grantee: | Paulo Roberto das Dores da Silva |
| Support type: | Scholarships in Brazil - Post-Doctorate |