Mitochondrial morphology in human fibroblasts and induced pluripotent stem cells in Leigh syndrome: A comparative analysis.

Mitochondria are dynamic organelles that regulate several vital cellular functions in both health and disease. Accurately quantifying different mitochondrial shapes using simple, affordable techniques remains challenging. We have previously developed a Mitochondrial Cellular Phenotype (MitoCellPhe) tool to quantify 24 different mitochondrial shapes, enabling sensitive analysis and quantification of mitochondrial phenotype in health, under stress, and in diseased conditions. This approach permits us to study the morphological changes, if any, associated with perturbations in the mitochondrial genome and function that contribute to mitochondrial diseases like Leigh Syndrome (LS), a fatal pediatric neurodegenerative and muscular disorder represented with different clinical phenotypes in infancy. Using images generated from normal and diseased fibroblasts and human induced pluripotent stem cells (hiPSCs) (undifferentiated), we have identified and characterized differences in morphologies between a healthy and diseased state in both undifferentiated hiPSCs and differentiated fibroblasts. These results will help us better understand the pathophysiology of devastating mitochondrial diseases like LS, especially in its early developmental stages.