Targeted protein degradation in mitochondria

Abstract

In this article, we describe targeted protein degradation technology specifically designed for mitochondria-localized proteins, with a primary focus on our own development. Our approach employs a bifunctional molecule comprised of a ligand for the target protein linked to an activator of caseinolytic protease P (ClpP), a mitochondria-localized protease complex. The degrader induces the selective degradation of target proteins by bringing target proteins and activated ClpP into proximity within the mitochondria. Furthermore, we discuss the advantages of this technology─specifically the direct recruitment of proteases─in comparison with other reported methods and outline future directions and prospects for this technology.