Mitochondrial membrane chromatography: Discovery of mitochondrial targeting modulators

Mitochondria are fundamental organelles that play a crucial role in cellular energy metabolism, substance metabolism, and various essential cellular signaling pathways. The dysfunction of mitochondria is significantly implicated in the onset and progression of aging, neurodegenerative diseases, metabolic disorders, and tumors, thereby rendering mitochondria-targeted regulation, a vital strategy for disease prevention and treatment. The recently developed mitochondrial membrane chromatography (MMC) technique, which immobilizes mitochondrial proteins as a chromatographic separation medium, has shown great potential for efficiently screening mitochondria-targeted modulators from complex compound library. In contrast to traditional screening methods, MMC has no need to purify mitochondrial proteins and can preserve its in situ and physiological conformation. Consequently, it presents broader application prospects for screening mitochondrial modulators as well as investigating receptor-ligand interactions involving any target protein associated with mitochondria. This review aims to elucidate the critical role of mitochondria in the development and progression of major chronic diseases, discuss recent advancements and applications of MMC, and propose future directions for MMC in the identification of novel mitochondrial modulators.