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Sunderland Repository records the research produced by the University of Sunderland including practice-based research and theses.

Mitochondrial protein interaction landscape of SS-31

Chavez, Juan D., Tang, Xiaoting, Campbell, Matthew, Reyes, Gustavo, Kramer, Philip A., Stuppard, Rudy, Keller, Andrew, Zhang, Huiliang, Rabinovitch, Peter S., Marcinek, David J. and Bruce, James E. (2020) Mitochondrial protein interaction landscape of SS-31. Proceedings of the National Academy of Sciences, 117 (26). pp. 15363-15373. ISSN 0027-8424

Item Type: Article


Mitochondrial dysfunction underlies the etiology of a broad spectrum of diseases including heart disease, cancer, neurodegenerative diseases, and the general aging process. Therapeutics that restore healthy mitochondrial function hold promise for treatment of these conditions. The synthetic tetrapeptide, elamipretide (SS-31), improves mitochondrial function, but mechanistic details of its pharmacological effects are unknown. Reportedly, SS-31 primarily interacts with the phospholipid cardiolipin in the inner mitochondrial membrane. Here we utilize chemical cross-linking with mass spectrometry to identify protein interactors of SS-31 in mitochondria. The SS-31-interacting proteins, all known cardiolipin binders, fall into two groups, those involved in ATP production through the oxidative phosphorylation pathway and those involved in 2-oxoglutarate metabolic processes. Residues cross-linked with SS-31 reveal binding regions that in many cases, are proximal to cardiolipin–protein interacting regions. These results offer a glimpse of the protein interaction landscape of SS-31 and provide mechanistic insight relevant to SS-31 mitochondrial therapy.

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Depositing User: Leah Maughan


Item ID: 13826
Identification Number:
ISSN: 0027-8424
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Users with ORCIDS

ORCID for Matthew Campbell: ORCID iD

Catalogue record

Date Deposited: 11 Aug 2021 13:16
Last Modified: 11 Aug 2021 13:16


Author: Matthew Campbell ORCID iD
Author: Juan D. Chavez
Author: Xiaoting Tang
Author: Gustavo Reyes
Author: Philip A. Kramer
Author: Rudy Stuppard
Author: Andrew Keller
Author: Huiliang Zhang
Author: Peter S. Rabinovitch
Author: David J. Marcinek
Author: James E. Bruce

University Divisions

Faculty of Health Sciences and Wellbeing > School of Nursing and Health Sciences

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