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bioRxiv · 10.1101/2024.09.12.612759

Age-dependent Changes in a Chaperone Complex in the Mouse Heart

Bhat, P. D.·Nalli, A.·Shoemaker, L.·Kwong, J. Q.·Krishnamurthy, P.·Benian, G. M.
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Abstract

The exquisitely organized sarcomere, the unit of contraction of striated muscle, is a stable structure with slow turnover of its components. The myosin chaperone UNC-45 and its binding partners, Hsp90 and Hsp70, are required for the initial folding of the myosin head domain and the assembly of myosin into thick filaments. There is increasing evidence that the UNC-45 system has an important role during aging to preserve sarcomere organization. Its decline may be a key factor in sarcopenia. Unlike skeletal muscle, the UNC-45 system in cardiac muscle in aging heart has not been examined extensively. Here we show that Unc45b and Hsp70 are localized to sarcomeric Z-discs in the mouse heart. We further show that during aging, there is a decline in the levels of myosin heavy chain, Unc-45b and Hsp70, but not Hsp90. While the decrease in Unc45b appears to be at the mRNA level, the decrease in the levels of myosin and Hsp70 were not at the mRNA but at the protein level. We have reported that in skeletal muscle, there is a decline in both Unc45b and Hsp90, and here we show that there is no such decline of Hsp70 in skeletal muscle. Hsp70 levels also did not decline with age in the brain or the liver. This heart-specific decrease of Hsp70 through its function as an Unc45b/Hsp70 complex might account for the age-dependent worsening of cardiomyopathies, and through Hsp70s multiple Unc-45b-independent functions, affect the folding and assembly of many other proteins in the aging heart.

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Bhat, P. D., Nalli, A., Shoemaker, L., Kwong, J. Q., Krishnamurthy, P., Benian, G. M.. 2024-09-12. Age-dependent Changes in a Chaperone Complex in the Mouse Heart. https://doi.org/10.1101/2024.09.12.612759

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