Perturbation of multiprotein complexes in skeletal muscle induces protective proteases in the CNS that degrade pathogenic proteins.

ABSTRACT: Many cellular functions rely on multiprotein complexes and their stoichiometric assembly. Reducing the levels of individual complex components can perturb this process and induce corrective stress responses. In addition to local outcomes, cellular stress in one tissue can induce long-distance responses in other tissues. Here, we used muscle-targeted RNAi to examine the systemic stress responses induced by muscle-specific genetic perturbation of four distinct multiprotein complexes: the sarcomere, mitochondrial respiratory complex I, proteasome, and VCP (valosin-containing protein) complex. Muscle-specific disruption of these four complexes produced largely overlapping transcriptional adaptations in the central nervous system (CNS), and these responses were centered on the upregulation of m

SUBMITTER: Rai M 

PROVIDER: S-EPMC12660746 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature