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bioRxiv · 10.64898/2025.12.20.694803

Evolutionarily Conserved T-tubule-Mitochondria Contacts in Striated Muscle

Qi, H.·Cao, L.·Li, A.·Wu, Q.·Wang, J.·Cao, M.·Liu, Z.·Sun, W.·Lai, Q.·Pan, W.
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Abstract

The intricate architecture of skeletal muscle is essential for its contractile function, with the spatial organization of organelles such as T-tubules and mitochondria playing a crucial role in maintaining muscle performance and health1,2. T-tubules propagate electrical signals deep into muscle fibers to ensure synchronous contraction, while mitochondria provide the necessary energy for muscle contraction3-5. Previous studies have extensively documented the interactions between T-tubules and the sarcoplasmic reticulum (SR), which are essential for excitation-contraction coupling6,7. However, the detailed spatial relationship between T-tubules and mitochondria has remained relatively unexplored. In this study, we utilized zebrafish and mice as model organisms to investigate the contacts between T-tubules and mitochondria. Using array tomography, deep learning-based analysis, and advanced microscopy techniques, we discovered extensive membrane contact sites, termed T-tubule-Mitochondria (TTM) contacts. These contacts are evolutionarily conserved across vertebrates, including skeletal and cardiac muscles. Our findings reveal a previously unrecognized, intimate spatial coupling between T-tubules and mitochondria, with significant implications for muscle physiology and pathology. Understanding these TTM contacts could provide new insights into the mechanisms underlying muscle function and the development of muscle-related diseases.

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Qi, H., Cao, L., Li, A., Wu, Q., Wang, J., Cao, M., Liu, Z., Sun, W., Lai, Q., Pan, W.. 2025-12-22. Evolutionarily Conserved T-tubule-Mitochondria Contacts in Striated Muscle. https://doi.org/10.64898/2025.12.20.694803

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