Mitochondrial Targeting and Imaging with Small Organic Conjugated Fluorophores: A Review

Abstract

The last decade has seen an increasingly large number of studies reporting on the development of novel small organic conjugated systems for mitochondrial imaging exploiting optical signal transduction pathways. Mitochondria are known to play a critical role in a number of key biological processes, including cellular metabolism. Importantly, irregularities on their working function are nowadays understood to be intimately linked to a range of clinical conditions, highlighting the importance of targeting mitochondria for therapeutic benefits. In this work we carry out an in-depth evaluation on the progress to date in the field to pave the way for the realization of superior alternatives to those currently existing. The manuscript is structured by commonly used chemical scaffolds and comprehensively covers key aspects factored in design strategies such as synthetic approaches as well as photophysical and biological characterization, to foster collaborative work among organic and physical chemists as well as cell biologists.

Keywords: bioimaging; fluorescence; mitochondria; optoelectronics; organic materials.

Figure 1

Representation of a eukaryotic cell highlighting the mitochondria in the cytoplasm as well as the structure of the inner and outer membranes.

Figure 2

Chemical structures and IUPAC numbering for commonly used fluorescent core motifs for mitochondrial imaging.

Figure 3

Simplified Jablonski diagram illustrating most common photophysical processes in organic molecules.

Figure 4

MCF7 intracellular distribution of 123 (250 nM, 0.163 μg mL⁻¹) and Mitotracker Red (250 nM, 0.133 μg mL⁻¹). Scale bar represents 50 μm. Adapted with permission. Copyright 2022, Wiley‐VCH.