Abstract Resistance exercise (RE) improves strength and muscle mass but concomitantly inflicts myofibrillar damage, necessitating efficient proteostatic restoration. The signaling and proteostatic processes distinguishing damaged and intact areas and the impact of different training states is incompletely understood. In this study, healthy subjects repeatedly executed acute high-intensity RE during a recurring and interrupted RE training regime to induce damage in untrained, adapted, and deadapted skeletal muscle. Xin actin-binding repeat-containing protein 1 (XIRP1) consistently marked RE-induced myofibrillar lesions, which were mitigated in trained muscle but rapidly reestablished upon detraining. Mass spectrometry-based proteome analyses of fractionated muscle biopsies revealed RE-induced cytoskeletal association of specific proteins, including small heat shock proteins (HSPBs) and chaperone-assisted selective autophagy (CASA) components. Changes in phosphorylation state of these proteins reflected skeletal muscle adaptation and deadaptation and coincided with altered localization. Functional studies in cell culture further identified the XIRP1A isoform as a novel proteostasis factor required for the recognition of CASA clients. Our study provides systemic insights into the molecular mechanisms mitigating myofibrillar damage in non-adapted and adapted human skeletal muscle exposed to intense mechanical stimulation.
Gehlert et al. (Wed,) studied this question.
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