A Lethal Defect of Mitochondrial and Peroxisomal Fission

TLDR

A newborn girl presents with microcephaly, abnormal brain development, optic atrophy, hypoplasia, persistent lactic acidaemia, and mildly elevated very‑long‑chain fatty acids, and the dynamin‑like protein 1 (DLP1) has been implicated in fission of mitochondria and peroxisomes. We identified a heterozygous dominant‑negative mutation in DLP1 that causes simultaneous fission defects in mitochondria and peroxisomes, and overexpression of the mutant protein reproduces the defect, indicating a class of diseases involving dual organelle dysfunction.

Abstract

We report on a newborn girl with microcephaly, abnormal brain development, optic atrophy and hypoplasia, persistent lactic acidemia, and a mildly elevated plasma concentration of very-long-chain fatty acids. We found a defect of the fission of both mitochondria and peroxisomes, as well as a heterozygous, dominant-negative mutation in the dynamin-like protein 1 gene (DLP1). The DLP1 protein has previously been implicated, in vitro, in the fission of both these organelles. Overexpression of the mutant DLP1 in control cells reproduced the fission defect. Our findings are representative of a class of disease characterized by defects in both mitochondria and peroxisomes.