%0 Journal Article
%T The myosin chaperone UNC-45 has an important role in maintaining the structure and function of muscle sarcomeres during adult aging.
%A Matheny CJ
%A Qadota H
%A Bailey AO
%A Valdebenito-Silva S
%A Oberhauser AF
%A Benian GM
%J Mol Biol Cell
%V 35
%N 7
%D 2024 Jul 1
%M 38809582
%F 3.612
%R 10.1091/mbc.E23-12-0488
%X C. elegans undergo age-dependent declines in muscle organization and function, similar to human sarcopenia. The chaperone UNC-45 is required to fold myosin heads after translation and is likely used for refolding after thermally- or chemically-induced unfolding. UNC-45's TPR region binds HSP-90 and its UCS domain binds myosin heads. We observe early onset sarcopenia when UNC-45 is reduced at the beginning of adulthood. There is sequential decline of HSP-90, UNC-45, and MHC B myosin. A mutation in age-1 delays sarcopenia and loss of HSP-90, UNC-45, and myosin. UNC-45 undergoes age-dependent phosphorylation, and mass spectrometry reveals phosphorylation of six serines and two threonines, seven of which occur in the UCS domain. Additional expression of UNC-45 results in maintenance of MHC B myosin and suppression of A-band disorganization in old animals. Our results suggest that increased expression or activity of UNC-45 might be a strategy for prevention or treatment of sarcopenia.