Beyond shape and energy - Define novel roles of mitochondria in cell migration – MitoMove

Mitochondria are multifunctional organelles central to cellular energy metabolism, calcium homeostasis, and redox balance. Beyond these classical roles, mitochondria are emerging as key regulators of cell motility, a fundamental process crucial for morphogenesis, immune response, and wound healing. However, the mechanistic link between mitochondria and cell migration remains poorly understood, with conflicting evidence regarding the role of mitochondrial dynamics in motility. The MitoMove project aims to elucidate how mitochondria influence cell motility by addressing three key objectives: (O1) determining the extent of mitochondrial relocalization and dynamic changes during migration, (O2) identifying the temporal relationship between lamellipodia formation and mitochondrial relocalization using optogenetic and organelle manipulation approaches, and (O3) assessing the functional specialization of lamellipodia-localized mitochondria.
Using cell models and zebrafish as an in vivo system, MitoMove will employ advanced live-cell imaging, genetic and pharmacological perturbations, and optogenetic tools to precisely manipulate mitochondrial positioning. Key deliverables include high-resolution spatial-temporal mapping of mitochondrial relocalization, manipulation of lamellipodia generation and mitochondrial behavior, and validation of 3D matrices for studying cell invasion. Further, the project will investigate the impact of excessive mitochondrial fusion/fission on migration, assess mitochondrial effects on focal adhesions, and establish zebrafish models to visualize mitochondrial relocalization and its effect on cell migration in vivo. Functional insights will be gained through optogenetic manipulation of lamellipodia, development of cellular models for population-level mitochondrial relocalization control, and mathematical modeling of how mitochondrial distribution effects cell motility. Finally, the use of various biosensors and unbiased proteomic analyses will characterize functionally specialized mitochondria within lamellipodia.

By integrating cell biology, optogenetics, and in vivo imaging, MitoMove will provide unprecedented mechanistic insights into mitochondrial involvement in cell motility. This research has broad implications for understanding the basic mechanisms of cellular migration in developmental biology.