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First‐in‐class cardiolipin‐protective compound as a therapeutic agent to restore mitochondrial bioenergetics
Open accessAbstract
A decline in energy is common in aging, and the restoration of mitochondrial bioenergetics may offer a common approach for the treatment of numerous age‐associated diseases. Cardiolipin is a unique phospholipid that is exclusively expressed on the inner mitochondrial membrane where it plays an important structural role in cristae formation and the organization of the respiratory complexes into supercomplexes for optimal oxidative phosphorylation. The interaction between cardiolipin and cytochrome c determines whether cytochrome c acts as an electron carrier or peroxidase. Cardiolipin peroxidation and depletion have been reported in a variety of pathological conditions associated with energy deficiency, and cardiolipin has been identified as a target for drug development. This review focuses on the discovery and development of the first cardiolipin‐protective compound as a therapeutic agent. SS‐31 is a member of the S zeto‐S chiller (SS) peptides known to selectively target the inner mitochondrial membrane. SS‐31 binds selectively to cardiolipin via electrostatic and hydrophobic interactions. By interacting with cardiolipin, SS‐31 prevents cardiolipin from converting cytochrome c into a peroxidase while protecting its electron carrying function. As a result, SS‐31 protects the structure of mitochondrial cristae and promotes oxidative phosphorylation. SS‐31 represents a new class of compounds that can recharge the cellular powerhouse and restore bioenergetics. Extensive animal studies have shown that targeting such a fundamental mechanism can benefit highly complex diseases that share a common pathogenesis of bioenergetics failure. This review summarizes the mechanisms of action and therapeutic potential of SS‐31 and provides an update of its clinical development programme. Linked Articles: This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue‐8
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“Furthermore, loss of phospholipids—particularly the cardiolipin of the IMM—exacerbates the pathology of AD [71].”
Background
Metadata
- Authors
- Szeto, H. H.
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2014-03-28
- Volume
- 171
- Issue
- 8
- Pages
- 2029-2050
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- OpenAlex
- W1722845210
- Cited by
- 548
- References
- 168
- FWCI
- 8.74
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.