Abstract

Mitochondria are a hub for multiple cellular functions and play an important role in cell aging and neurodegenerative diseases. Mitochondria are also very dynamic structures with fluctuating morphologic transitions in response to cellular and environmental perturbations. While there have been studies investigating the pathways and conditions that alter mitochondrial morphology, the connections between these morphological changes and gene expression regulation are still poorly understood. We recently found that cells use translation elongation and mitochondrial spatial organization to fine-tune mitochondria-specific gene expression. Our single-molecule visualization techniques showed that changes in mitochondrial volume fraction affected the localization of certain nuclear-encoded mRNAs to the surface of the mitochondria (Tsuboi* et al., 2020). I will discuss general principles that underlie the control of gene expression through mitochondrial morphological change during cellular aging and fluctuating environmental conditions (Khan et al., 2024). I will further introduce our recent progress in image-based drug screening methodology.