Triggering mitophagy with far-red fluorescent photosensitizers

Cells identify defective mitochondria and eliminate them through mitophagy: this allows cells to rid themselves of unwanted stress to maintain health and avoid the activation of cell death. One approach to experimentally investigate mitophagy is through the use of mitochondrial photosensitizers, which when coupled with light allows one to precisely control mitochondrial damage with spatial and temporal precision. Here we report three far-red fluorophores that can be used as robust mitochondrial photosensitizers to initiate mitophagy. The dyes offer maximal compatibility with multi-color live-cell imaging, as they do not spectrally overlap with commonly used fluorescent proteins. Through the use of these far-red fluorescent photosensitizers we found that mitophagic engulfment and mitophagosome maturation rates are highly correlated with the cellular Parkin-labeled mitochondria levels. This may represent a protective cellular mechanism to avoid membrane and lysosome depletion during mitophagy.