Poly (A) tail length of human mitochondrial mRNAs is tissue-specific and a mutation in LRPPRC results in transcript-specific patterns of deadenylation.

Mutations in LRPPRC cause Leigh Syndrome French Canadian (LSFC), an early onset neurodegenerative disease, with differential tissue involvement. The molecular basis for tissue specificity in this disease remains unknown. LRPPRC, an RNA binding protein, forms a stable complex with SLIRP, which binds to, and stabilizes mitochondrial mRNAs.

Loss of hepatic LRPPRC alters mitochondrial bioenergetics, regulation of permeability transition and trans-membrane ROS diffusion.

The French-Canadian variant of Leigh Syndrome (LSFC) is an autosomal recessive oxidative phosphorylation (OXPHOS) disorder caused by a mutation in LRPPRC, coding for a protein involved in the stability of mitochondrially-encoded mRNAs. Low levels of LRPPRC are present in all patient tissues, but result in a disproportionately severe OXPHOS defect in the brain and liver, leading to unpredictable subacute metabolic crises. To investigate the impact of the OXPHOS defect in the liver, we analyzed the mitochondrial phenotype in mice harboring an hepatocyte-specific inactivation of Lrpprc.