LONP1 de novo dominant mutation causes mitochondrial encephalopathy with loss of LONP1 chaperone activity and excessive LONP1 proteolytic activity.

ABSTRACT: LONP1 is an ATP-dependent protease and chaperone that plays multiple vital roles in mitochondria. LONP1 is essential for mitochondrial homeostasis due to its role in maintenance of the mitochondrial genome and its central role in regulating mitochondrial processes such as oxidative phosphorylation, mitophagy, and heme biosynthesis. Bi-allelic LONP1 mutations have been reported to cause a constellation of clinical presentations. We report a patient heterozygous for a de novo mutation in LONP1: c.901C>T,p.R301W presenting as a neonate with seizures, encephalopathy, pachygyria and microcephaly. Assays of respiratory chain activity in muscle showed complex II-III function at 8% of control. Functional studies in patient fibroblasts showed a signature of dysfunction that included significant dec

SUBMITTER: Besse A 

PROVIDER: S-EPMC8628847 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature