PARL deficiency in mouse causes Complex III defects, coenzyme Q depletion, and Leigh-like syndrome.

ABSTRACT: The mitochondrial intramembrane rhomboid protease PARL has been implicated in diverse functions in vitro, but its physiological role in vivo remains unclear. Here we show that Parl ablation in mouse causes a necrotizing encephalomyelopathy similar to Leigh syndrome, a mitochondrial disease characterized by disrupted energy production. Mice with conditional PARL deficiency in the nervous system, but not in muscle, develop a similar phenotype as germline Parl KOs, demonstrating the vital role of PARL in neurological homeostasis. Genetic modification of two major PARL substrates, PINK1 and PGAM5, do not modify this severe neurological phenotype. Parl^-/- brain mitochondria are affected by progressive ultrastructural changes and by defects in Complex III (

SUBMITTER: Spinazzi M 

PROVIDER: S-EPMC6320509 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature