biorxiv2026-11-03score 95
Bacterial LplA plus lipoic acid rescues lethal Lipt1 myopathy by restoring mitochondrial lipoylation and OXPHOS
In a muscle-specific Lipt1-deficient mouse that survives embryonic lethality, adeno-associated virus (AAV) delivery of bacterial lipoate protein ligase A (LplA) plus lipoic acid reconstitutes mitochondrial protein lipoylation and oxidative phosphorylation in situ. That energetic rescue suppresses PI3K-Akt hyperactivation, restores autophagic clearance, recovers motor function, and reverses hypertrophic cardiomyopathy. The intervention bypasses the mammalian endogenous lipoylation pathway rather than repairing it.
