Live-Imaging Readouts and Cell Models for Phenotypic Profiling of Mitochondrial Function

Mitochondria are best known as the powerhouses of the cells but their cellular role goes far beyond energy production; among others, they have a pivotal function in cellular calcium and redox homeostasis. Mitochondrial dysfunction is often associated with severe and relatively rare disorders with an unmet therapeutic need. Given their central integrating role in multiple cellular pathways, mitochondrial dysfunction is also relevant in the pathogenesis of various other, more common, human pathologies. Here we discuss how live-cell high content microscopy can be used for image-based phenotypic profiling to assess mitochondrial (dys) function. From this perspective, we discuss a selection of live-cell fluorescent reporters and imaging strategies and discuss the pros/cons of human cell models in mitochondrial research. We also present an overview of live-cell high content microscopy applications used to detect disease-associated cellular phenotypes and perform cell-based drug screening.