Key result
This review summarizes the mechanisms of protein quality control in the sarcomere, highlighting the roles of the proteasome, autophagy, heat shock proteins, and proteases in titin protection and degradation.
Why the study?
The molecular processes involved in titin turnover and its relationship with protein quality control are not fully understood despite its role in muscle contraction and disease.
The review highlights the critical role of protein quality control mechanisms, including the ubiquitin-proteasome system and autophagy, in maintaining titin homeostasis and their implications for cardiac and skeletal muscle diseases.
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Titin proteostasis pathways merit targeted study in myopathies; leaves open therapeutic translation in sarcomeric disease.
Sarcomeres are mainly composed of filament and signaling proteins and are the smallest molecular units of muscle contraction and relaxation. The sarcomere protein titin serves as a molecular spring whose stiffness mediates myofilament extensibility in skeletal and cardiac muscle. Due to the enormous size of titin and its tight integration into the sarcomere, the incorporation and degradation of the titin filament is a highly complex task. The details of the molecular processes involved in titin turnover are not fully understood, but the involvement of different intracellular degradation mechanisms has recently been described. This review summarizes the current state of research with particular emphasis on the relationship between titin and protein quality control. We highlight the involvement of the proteasome, autophagy, heat shock proteins, and proteases in the protection and degradation of titin in heart and skeletal muscle. Because the fine-tuned balance of degradation and protein expression can be disrupted under pathological conditions, the review also provides an overview of previously known perturbations in protein quality control and discusses how these affect sarcomeric proteins, and titin in particular, in various disease states.
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Kötter et al. (2022) conducted a review in Sarcomere protein quality control and disease development. Protein quality control mechanisms (proteasome, autophagy, proteases, heat shock proteins) was evaluated. This review summarizes the mechanisms of protein quality control in the sarcomere, highlighting the roles of the proteasome, autophagy, heat shock proteins, and proteases in titin protection and degradation.
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