Defective mitochondrial translation caused by a ribosomal protein (MRPS16) mutation

TLDR

The mitochondrial respiratory chain consists of 85 subunits, 13 encoded by mtDNA, whose synthesis depends on numerous nuclear‑encoded proteins involved in DNA replication, transcription, and a specialized mitochondrial translation system. The study proposes a new class of mitochondrial respiratory chain disorders caused by mutations in nuclear‑encoded components of the mitochondrial translation machinery. Using pulse‑labeling of mitochondrial proteins, the authors identified a nonsense mutation in MRPS16 that reduces 12S rRNA levels and impairs mitochondrial translation. The patient exhibited agenesis of the corpus callosum, dysmorphism, fatal neonatal lactic acidosis, and markedly reduced complex I and IV activity, reflecting a generalized mitochondrial translation defect. Ann Neurol 2004;56:734–738.

Abstract

Abstract The mitochondrial respiratory chain comprises 85 subunits, 13 of which are mitochondrial encoded. The synthesis of these 13 proteins requires many nuclear‐encoded proteins that participate in mitochondrial DNA replication, transcript production, and a distinctive mitochondrial translation apparatus. We report a patient with agenesis of corpus callosum, dysmorphism, and fatal neonatal lactic acidosis with markedly decreased complex I and IV activity in muscle and liver and a generalized mitochondrial translation defect identified in pulse‐label experiments. The defect was associated with marked reduction of the 12S rRNA transcript level likely attributed to a nonsense mutation in the MRPS16 gene. A new group of mitochondrial respiratory chain disorders is proposed, resulting from mutations in nuclear encoded components of the mitochondrial translation apparatus. Ann Neurol 2004;56:734–738