Study summary · research use only
Mitochondrial protein interaction landscape of SS-31
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this study (species not specified), researchers used chemical cross-linking combined with mass spectrometry to identify proteins that interact with the synthetic tetrapeptide elamipretide (SS-31) in mitochondria. The abstract reports SS-31 as described elsewhere as primarily interacting with the phospholipid cardiolipin in the inner mitochondrial membrane, and that the newly identified SS-31-interacting proteins were all known cardiolipin binders, falling into two groups: those involved in ATP production through oxidative phosphorylation and those involved in 2-oxoglutarate metabolic processes. Residues cross-linked with SS-31 were reported to be located near cardiolipin-protein interacting regions. The authors describe these findings as offering insight into the protein interaction landscape of SS-31 relevant to its proposed mitochondrial activity.
Abstract
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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