Mitochondria-targeting peptides and peptidomimetics: recent progress and design principles.

Abstract

Mitochondria are multifunctional subcellular organelles whose operations encompass energy production, signal transduction, and metabolic regulation. Given their wide range of roles, they have been studied extensively as a potential therapeutic target for the treatment of various diseases including cancer, diabetes, and neurodegenerative diseases. Mitochondria-mediated pathways have been identified as promising targets in the context of these diseases. However, the delivery of specific probes and drugs to the mitochondria remains as one of the major problems yet to be solved. Over the past decade, many efforts have been made to develop mitochondria-targeted delivery methods based on the membrane characteristics and the protein import machinery of mitochondria. While various methods utilizing small molecules to polymeric particles have been introduced, it is notable that many of these compounds share common structural elements and physicochemical properties for optimal selectivity and efficiency. In this perspective, we will overview most recently developed mitochondria-targeting peptides and peptidomimetics to outline the key aspects of structural requirement and design principle. We will also discuss successful and potential applications of mitochondrial delivery to assess opportunities and challenges in mitochondria-targeting.