Journal Article

Cooperative control of striated muscle mass and metabolism by MuRF1 and MuRF2

Labeit, Dietmar, Witt, Christian C, Lerche, Stefanie, Back, Walter, Witt, Stephanie H, Labeit, Siegfried

2008

Overview

The muscle‐specific RING finger proteins MuRF1 and MuRF2 have been proposed to regulate protein degradation and gene expression in muscle tissues. We have tested the in vivo roles of MuRF1 and MuRF2 for muscle metabolism by using knockout (KO) mouse models. Single MuRF1 and MuRF2 KO mice are healthy and have normal muscles. Double knockout (dKO) mice obtained by the inactivation of all four MuRF1 and MuRF2 alleles developed extreme cardiac and milder skeletal muscle hypertrophy. Muscle hypertrophy in dKO mice was maintained throughout the murine life span and was associated with chronically activated muscle protein synthesis. During ageing (months 4–18), skeletal muscle mass remained stable, whereas body fat content did not increase in dKO mice as compared with wild‐type controls. Other catabolic factors such as MAFbox/atrogin1 were expressed at normal levels and did not respond to or prevent muscle hypertrophy in dKO mice. Thus, combined inhibition of MuRF1/MuRF2 could provide a potent strategy to stimulate striated muscles anabolically and to protect muscles from sarcopenia during ageing.

• Publisher: John Wiley & Sons, Ltd,Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
• Subject: Adaptor Proteins, Signal Transducing - genetics / Adaptor Proteins, Signal Transducing - metabolism / Animals / Biodegradation / Blotting, Western / Carps - metabolism / Cellular biology / Female / Gene expression / Gene Expression Profiling / Heat-Shock Proteins - genetics / Heat-Shock Proteins - metabolism / Homeodomain Proteins - genetics / Homeodomain Proteins - metabolism / Inactivation / Life span / LIM-Homeodomain Proteins / Male / Metabolism / Mice / Mice, Inbred C57BL / Mice, Inbred Strains / Mice, Knockout / Microscopy, Electron, Transmission / Microscopy, Fluorescence / Molecular biology / Muscle Cells - cytology / Muscle Cells - metabolism / muscle hypertrophy and atrophy / Muscle Proteins - genetics / Muscle Proteins - metabolism / Muscle Proteins - physiology / Muscle, Skeletal - cytology / Muscle, Skeletal - metabolism / Muscle, Skeletal - ultrastructure / Muscle, Striated - cytology / Muscle, Striated - metabolism / Muscle, Striated - ultrastructure / Muscles / Muscular Diseases - genetics / Muscular Diseases - metabolism / Muscular Diseases - pathology / Muscular system / Myocardium - cytology / Myocardium - metabolism / Myocardium - ultrastructure / Protein Binding / Protein synthesis / Proteins / Rodents / Sequestosome-1 Protein / Signal Transduction - genetics / Signal Transduction - physiology / striated muscle / Transcription Factors - genetics / Transcription Factors - metabolism / Tripartite Motif Proteins / ubiquitin ligases MuRF1 and MuRF2 / Ubiquitin-Protein Ligases - genetics / Ubiquitin-Protein Ligases - metabolism / Ubiquitin-Protein Ligases - physiology / Z-disks