Quantitative imaging and phenotyping of mitochondrial morphology in live cells

Mitochondria are vital cellular organelles for life due to their central role in energy production and the regulation of cellular metabolism. Their morphology is closely linked to their function, and any dysfunction of the mitochondria can have major consequences for their shape as well as for the health of cells, tissues and organisms. Their ability to transition between various structural and functional states make them excellent organelles for monitoring cell health. Healthy mitochondria are usually mobile, tubular and interconnected, whereas cells under stress or entering apoptosis often display swollen or fragmented mitochondria, marked by concurrent disruption of metabolism and excess production of reactive oxygen species. Quantitative imaging-based assessment of mitochondrial morphology can therefore provide valuable insights into tissue physiology, pathology and damage. Over the last few years, we have developed innovative computerized methods that enable accurate, multiscale, fast and cost-effective analysis of mitochondrial shape and network architecture from confocal fluorescence images. The core component of the workflow typically involves in-house, proprietary software (with APP deposit) that has evolved through successive versions (MitoShape, MitoTouch and the most recent, AI-driven version, MitoRadar). We have applied our fully automated image analysis pipeline (MITOMATICS) on rich datasets collected from living human cells to monitor pathophysiological conditions, as well as the harmfulness and/or toxicity of environmental pollutants. Our technology and software tools have potential for applications in research areas such as predictive and environmental toxicology, high-throughput drug screening, and high-content phenotypic screening