Optical imaging probes for mitochondrial metabolism: Mechanism, design and frontier applications

Mitochondria are pivotal organelles in eukaryotic cells, intricately linked to cellular functions and energy metabolism. Mitochondrial metabolic processes can be induced by intracellular or extracellular factors, leading to alterations in metabolite levels and subsequent mitochondrial dysfunction and related diseases. Consequently, developing noninvasive, real-time imaging techniques capable of monitoring mitochondrial metabolites in complex biological systems is crucial for elucidating the relationship between mitochondrial metabolism and disease mechanisms. Optical imaging technology, with its advantages of noninvasiveness and high spatiotemporal resolution, has emerged as a powerful tool for studying mitochondrial metabolic activities. This review begins with the structure and energy metabolism of mitochondria, discussing the correlation between metabolites and mitochondrial activity. It then focuses on the emission mechanisms and functional design strategies of various optical materials, including small-molecule fluorophores, semiconducting polymer nanoparticles (SPNs), aggregation-induced emission (AIE) materials, and lanthanide metal complexes, while summarizing their applications in detecting mitochondrial metabolites. Finally, the limitations and challenges of optical imaging in clinical translation are discussed.