The effects of CISD2 knockout on mitochondrial morphological subtypes in 3D micrographs of mouse epidermal tissues

Abstract

CISD2, CDGSH Iron Sulfur Domain 2, is a gene associated with Wolfram Syndrome. Lack of CISD2 results in premature aging. Such defects can cause skin thinning and activate mitophagy and mitochondrial disorder. However, the effects of CISD2 knockout on mitochondrial dynamics of skin tissues are unclear because lack of 3D mitochondrial morphological analysis in tissues. In this paper, 3D micrographs of mouse epidermal tissue in normal and premature aging (CISD2 knockout) mice expressing Dendra2-mito, which visualized mitochondrial morphology, were analyzed. Cells at different depths of skin layers were analyzed separately. Mitochondrial objects were segmented by MicroP, and then used for acquiring 3D morphological features. Features have been normalized to cluster mitochondrial objects into mitochondrial subtypes by X-means. There were total 7 mitochondrial morphological subtypes in epidermal tissue, and the distributions of each subtype between normal and premature ageing epidermal cells were different.