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Ribosome–Mitochondria Coupling Defines Translational Capacity as a Limiting Determinant of Cardiac Metabolic Output

This article is a preprint and has not been certified by peer review.

Authors

    Xiaofang Zhang,  
    Xiaofang Zhang
    • the First Affiliated Hospital of Jinan University
    Qiaxin Xu,  
    Qiaxin Xu
    Haowen Ye,  
    Haowen Ye
    Shishi Li,  
    Shishi Li
    Jiaxin Wang,  
    Jiaxin Wang
    Tianqi Duo,  
    Tianqi Duo
    • First Affiliated Hospital of Jinan University
    Na Wang,  
    Na Wang
    • First Affiliated Hospital of Jinan University
    Luchen Shan,  
    Luchen Shan
    • Jinan University
    Wenyue Li,  
    Wenyue Li
    Jiali Fu,  
    Jiali Fu
    • First Affiliated Hospital of Jinan University
    Jingde Han,  
    Jingde Han
    Zhou Yang,  
    Zhou Yang
    • First Affiliated Hospital of Jinan University
    Yanjie Lu,  
    Yanjie Lu
    Jun Guo,  
    Jun Guo
    Baofeng Yang,  
    Baofeng Yang
    • Harbin Medical University
    Jinghao Wang,  
    Jinghao Wang
    Zhiguo Wang
    Zhiguo Wang
    • the First Affiliated Hospital of Jinan University
Categories
Molecular Biology
Keywords
proteostasis; ribosomal proteins (RPS5/MRPS5); mitochondria–rough endoplasmic reticulum contact sites

Abstract

The mechanisms that define the metabolic capacity of the heart remain incompletely understood. Here, we identify translational capacity as a rate-limiting determinant of cardiac metabolic output, mediated by a ribosome–mitochondria coupling axis linking cytosolic and mitochondrial protein synthesis. Integrated transcriptomic and proteomic analyses reveal extensive discordance between mRNA and protein abundance, accompanied by suppression of global protein synthesis, reduced ribosome biogenesis, and disruption of proteostasis. We identify a ribosome–mitochondria coupling axis in which the cytosolic ribosomal protein RPS5 regulates the abundance and mitochondrial localization of MRPS5, a component of the mitochondrial ribosome. This process occurs in association with endoplasmic reticulum–mitochondria contact sites and links cytosolic translation to mitochondrial protein synthesis. Perturbation of this axis is associated with reduced expression of metabolic enzymes and impaired mitochondrial function. Conversely, restoration of RPS5 or MRPS5 improves mitochondrial activity and cardiac performance in vivo. These findings suggest that translational capacity contributes to metabolic homeostasis and reveal a spatially organized mechanism linking protein synthesis to mitochondrial function in the diabetic heart.

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DOI:

https://doi.org/10.65215/LTSpreprints.2026.05.07.000232

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Posted

2026-05-07

How to Cite

Zhang, X., Xu, Q., Ye, H., Li, S., Wang, J., Duo, T., Wang, N., Shan, L., Li, W., Fu, J., Han, J., Yang, Z., Lu, Y., Guo, J., Yang, B., Wang, J., & Wang, Z. (2026). Ribosome–Mitochondria Coupling Defines Translational Capacity as a Limiting Determinant of Cardiac Metabolic Output. LangTaoSha Preprint Server. https://doi.org/10.65215/LTSpreprints.2026.05.07.000232

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