An ALLO-1-associated network links mitochondrial quality control to functional recovery in structurally compromised muscle.

Abstract

Muscle function can recover before damaged contractile structures are fully repaired, but the mechanisms enabling this recovery remain poorly understood. Using a temperature-sensitive Caenorhabditis elegans model of UNC-45 dysfunction, in which impaired myosin chaperoning triggers muscle proteotoxic stress and reversible paralysis, we show that coordinated movement recovers while sarcomere disorganisation persists. Quantitative proteomics identified ALLO-1, a selective-autophagy receptor previously characterised for paternal organelle clearance during embryogenesis, as induced during recovery from UNC-45dependent muscle stress. Functional and proteomic analyses revealed an ALLO-1-associated regulatory network comprising IKKE-1, SIP-1, DIM-1 and CAR-1 that modulates mitochondrial stress responses and muscle recovery. Loss of ALLO-1 or its associated factors altered mitochondrial homoeostasis and delayed functional recovery, whereas muscle-specific ALLO-1a restoration improved recovery, preserved mitochondrial network integrity, and modulated mitochondrial turnover despite reduced respiratory capacity. These findings identify ALLO-1 as a regulator of mitochondrial stress adaptation that enables functional recovery before completing structural repair.