Unlocking mitochondrial drug targets: The importance of mitochondrial transport proteins

• Published in: Acta Physiologica 2024-06, Vol.240 (6), p.e14150-n/a
• Main Authors: Hoogstraten, Charlotte A., Schirris, Tom J. J., Russel, Frans G. M.
• Format: Article
• Language: English
• Subjects: Animals; carrier proteins; Carrier Proteins - metabolism; Drug development; drugs; efficacy and safety; Humans; inner mitochondrial membrane; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial Proteins - metabolism; on‐ and off‐target; Organelles; Protein transport; Therapeutic targets
• ISSN: 1748-1708; 1748-1716; 1748-1716
• DOI: 10.1111/apha.14150

A disturbed mitochondrial function contributes to the pathology of many common diseases. These organelles are therefore important therapeutic targets. On the contrary, many adverse effects of drugs can be explained by a mitochondrial off‐target effect, in particular, due to an interaction with carrier proteins in the inner membrane. Yet this class of transport proteins remains underappreciated and understudied. The aim of this review is to provide a deeper understanding of the role of mitochondrial carriers in health and disease and their significance as drug targets. We present literature‐based evidence that mitochondrial carrier proteins are associated with prevalent diseases and emphasize their potential as drug (off‐)target sites by summarizing known mitochondrial drug–transporter interactions. Studying these carriers will enhance our knowledge of mitochondrial drug on‐ and off‐targets and provide opportunities to further improve the efficacy and safety of drugs.