Friday, April 4, 2025
4/4/2025
Mitochondrial function regulates ROS-mediated patterning following injury - Abstract Mitochondria are critical for generating energy. Recently a new role for mitochondria in controlling metabolic signaling through generation of reactive oxygen species (ROS) has come to light. ROS has also recently come into the spotlight as being a critical signaling axis for limb regeneration, and while mitochondrial signaling has been well-established in cell homeostasis, the role of mitochondrial generated ROS and its downstream mechanisms in controlling regeneration is not clear. Using the established mouse digit tip amputation regeneration model, spatial transcriptomics, and unique transgenic mice, we uncovered a unique role for two mitochondrial regulatory proteins, BNIP3 and NIX, in regeneration. Our preliminary findings support that regeneration is dependent on the mitochondrial regulation protein BNIP3, and that this protein supports ROS- generated, directional morphogenetic signaling gradients from the wound epithelium. Further, our preliminary data support that a second mitochondrial regulatory protein, NIX, serves to support blastema maturation and differentiation, a structure critical to regenerating the bone and soft tissue. We hypothesize that BNIP3 and NIX function in a spatially distinct relationship where NIX supports differentiation in the blastema in response to adjacent signaling gradients generated by BNIP3 in the wound epithelium. This project would provide the first evidence of a BNIP3/NIX signaling access in injury, implicating mitochondrial function and mitophagy as spatial regulators of the regeneration process, and giving a broader context to a mitochondrial homeostasis mechanism that is salient to many fields.
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