USF-LVHN SELECT
Ankyrin-B modulates mitochondrial fission in skeletal muscle and is required for optimal endurance exercise capacity.
Publication/Presentation Date
8-25-2025
Abstract
Mitochondrial dynamics enable cellular adaptation to fluctuations in energy demand, such as those imposed on skeletal muscle by exercise, metabolic disorders, or aging. Here, we report a novel pathway that modulates mitochondria dynamics in skeletal muscle involving the scaffolding protein ankyrin-B. Rare variants in ankyrin-B, encoded by ANK2, increase risk for cardio-metabolic syndrome in humans and mice. We show that mice selectively lacking skeletal muscle ankyrin-B have reduced endurance exercise capacity without alterations in muscle strength or systemic glucose regulation. Muscle fibers in these mice have increased oxidative stress, reduced fatty acid oxidation, and enlarged and hyperconnected mitochondria. We found that ankyrin-B interacts with and is required for efficient mitochondria recruitment of fission modulators and sarcoplasmic reticulum-mitochondria coupling. Thus, we conclude that ankyrin-B enables substrate adaptability and bioenergetic homeostasis under energetic stress, and exercise capacity by promoting efficient mitochondrial fission in skeletal muscle.
Volume
16
Issue
1
First Page
7671
Last Page
7671
ISSN
2041-1723
Published In/Presented At
Voos, K. M., Tzeng, J., Patel, P., Rubinsky, S., Choi, H. E., Pharr, T., Sookram, S., Baur, J. A., Soderblom, E. J., & Lorenzo, D. N. (2025). Ankyrin-B modulates mitochondrial fission in skeletal muscle and is required for optimal endurance exercise capacity. Nature communications, 16(1), 7671. https://doi.org/10.1038/s41467-025-62977-3
Disciplines
Medical Education | Medicine and Health Sciences
PubMedID
40854882
Department(s)
USF-LVHN SELECT Program, USF-LVHN SELECT Program Students
Document Type
Article