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Insertion of human mtHsp70 (mortalin) into liposomes resembling mitochondrial membrane.
Author(s) -
Dores Silva Paulo Roberto,
Cauvi David M.,
Borges Julio Cesar,
De Maio Antonio
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.793.17
Subject(s) - liposome , popc , mitochondrion , cytosol , cardiolipin , chaperone (clinical) , inner mitochondrial membrane , cytoplasm , hsp70 , microbiology and biotechnology , intracellular , biochemistry , recombinant dna , chemistry , membrane , mitochondrial membrane transport protein , biology , lipid bilayer , heat shock protein , gene , phospholipid , medicine , pathology , enzyme
Heat shock proteins (hsp) are important components of the cellular chaperone pool, playing an important role in protein folding, intracellular traffic, and degradation among others. The Hsp70 family of hsp present a 40–60% sequence identity among its prokaryotic and eukaryotic members. The human mitochondrial Hsp70 (mtHsp70), also named mortalin, is mainly involved in the transport of proteins from the cytosol into the mitochondrion matrix. It is also present in the cytoplasm where it is involved in the p53 sequestration. Prior studies have shown that the human Hsp70 and Hsc70 have an unusual capacity for interacting with lipid membranes opening ion conductance pathways. Since mtHsp70/mortalin is a key player in the translocation of polypeptides across the mitochondrial membrane, we investigate whether this protein could also get inserted into lipid membranes. To test this hypothesis, we performed interactions studies with recombinant mtHsp70/mortalin and liposomes, resembling the composition of the mitochondrial membrane. Recombinant human mtHsp70/mortalin was incubated with liposomes (100nm) made of lipids contained in the mitochondrial membrane: palmitoyl‐oleoyl phosphocholine (POPC), palmitoyl‐oleoyl phosphoserine (POPS), and palmitoyl‐oleoyl phosphoethanolamine (POPE), and cardiolipin (CL). In addition, the effect of the co‐chaperone hHep1 on liposome insertion was analyzed. MtHsp70/mortalin displayed a great predilection for POPS and CL and a low affinity for POPC and POPE, suggesting that the proteins that it has high specificity for are negatively charged lipids. The interaction of mtHsp70/mortalin with CL may be very relevant for the interaction with the mitochondrial membrane that is enriched in CL (up to 15% of total lipids). In contrast, the co‐chaperone hHep1 interacted with liposomes made of all the lipids with high prominence for POPC. In all, our data have shown that mtHsp70/mortalin, as well as other human Hsp70s, are prone to interact with membranes and that perhaps is also the case of the inner mitochondrial membrane and the CL lipid plays a central role in this interaction. Support or Funding Information This work was supported by National Institutes of Health (NIH) Grants R01 GM098455‐04 and R01 GM114473‐01 and FAPESP process: 2016/22477‐1 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .