Mitochondrial form and function in health and disease

Mitochondria are essential organelles whose morphology varies tremendously across cell types and tissues. Balanced fusion and fission events shape mitochondria to meet metabolic demands and to ensure removal of damaged organelles. The dynamism of mitochondria is highlighted by the dramatic changes in morphology they undergo in response to metabolic inputs. The morphology of mitochondria is inextricably linked to its many essential functions in the cell and we are interested in understanding the relationship between mitochondrial shape changes and metabolism in the context of acquired and inborn human diseases. We recently established a high-throughput imaging pipeline using supervised machine learning (ML) to perform unbiased, quantitative mitochondrial morphology analysis that was coupled with a bespoke siRNA library targeting the entire known mitochondrial proteome (1531 genes), providing a detailed phenotypic screening of human fibroblasts. In my talk, I will discuss the insights we have made regarding the regulation of mitochondrial morphology and its importance for cellular homeostasis.