A lethal defect of mitochondrial and peroxisomal fission.
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.
Waterham
Hans R
HR
Department of Pediatrics, Academic Medical Center, Amsterdam, The Netherlands. h.r.waterham@amc.uva.nl
Koster
Janet
J
van Roermund
Carlo W T
CW
Mooyer
Petra A W
PA
Wanders
Ronald J A
RJ
Leonard
James V
JV
D000015:Abnormalities, Multiple / Q000235:genetics*; D000140:Acidosis, Lactic / Q000235:genetics; D034281:Dynamins; D005124:Eye Abnormalities / Q000235:genetics; D017809:Fatal Outcome; D005227:Fatty Acids / Q000097:blood; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D020558:GTP Phosphohydrolases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008831:Microcephaly / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D009123:Muscle Hypotonia / Q000235:genetics; D009154:Mutation; D016366:Open Reading Frames / Q000235:genetics; D020675:Peroxisomes / Q000378:metabolism / Q000502:physiology*; D017422:Sequence Analysis, DNA
D005227:Fatty Acids; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins