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 Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2019
• End date: September 30, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Julio Cesar Borges
• Grantee: Milene Nóbrega de Oliveira Moritz
• Host 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
• Associated scholarship(s): 21/12775-3 - The role of hHep1/Hsp70s in protein quality control and the regulation of condensate dynamics upon proteotoxic stress, BE.EP.PD

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. (AU)