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Cellular functional study of high molecular weight oligomers of mortaline and the effects of mitochondrial co-chaperones on their structure

Grant number: 19/22422-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): December 01, 2019
Effective date (End): November 30, 2021
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Julio Cesar Borges
Grantee:Milene Nóbrega de Oliveira Moritz
Home Institution: Instituto de Química de São Carlos (IQSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
Associated research grant:17/26131-5 - The chaperome: study of the relationship of the structure of its components and the maintenance of proteostasis, AP.TEM

Abstract

The main objective of this research is the cellular study of human mortalin together with co-chaperones and chaperones that possibly assists it in the process of importation and folding of cytoplasmic proteins. Experiments from our group (in submission) indicate that mortalin and Hsp70-1A undergo temperature-induced oligomerization and that thermal oligomers (or supramolecular complexes) have secondary structure, ATPase activity, liposome-interacting ability, block A²1-42 peptide oligomerization and are not cytotoxic (article in preparation). Interestingly, Hsp70 oligomers and isoform aggregates are observed in cells and these are hypothesized to be cellular Hsp70 deposits. In this sense, the cellular characterization of these oligomers, including their cell dynamics, and the evaluation of possible remodeling factors and Hsp70 recruitment of oligomers can have a great scientific importance. The objective of this project is also to characterize the interaction of mortalin with co-chaperones residing in mitochondria (such as J-proteins hDjC20 and co-chaperones hHep1, hGrpE#1e and hGrpE#2). Additionally, the objective is to study factors (co-chaperones and nucleotides, among others) that support remodeling of Hsp70 supramolecular complexes into smaller particles or even monomers.