Optineurin binding to the novel interacting partner Junction plakoglobin prevents muscle atrophy in mice.

ABSTRACT: Skeletal muscle atrophy is a debilitating condition that significantly affects patients' quality of life and prognosis, yet its underlying mechanisms remain poorly understood. Here, we identify Optineurin (OPTN) as an active regulator for maintenance of muscle homeostasis during muscle atrophy. Knockdown (KD) of Optn induces muscle atrophy, while overexpression of Optn alleviated dexamethasone-induced muscle atrophy in mice. Mechanistically, we for the first time identified Junction plakoglobin (JUP) as a novel interacting partner of OPTN. OPTN alleviates muscle atrophy in a JUP-dependent manner, corroborating JUP as the downstream effector of OPTN-mediated muscle atrophy. RNA-seq analysis revealed that PI3K-AKT pathway is markedly downregulated in Optn-KD muscle, and pharmacological activ

SUBMITTER: Shi XC 

PROVIDER: S-EPMC12851441 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature