Journal
MOLECULAR GENETICS AND METABOLISM
Volume 100, Issue 2, Pages 149-154Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymgme.2010.03.005
Keywords
Optic atrophy; OPA3; 3-Methylglutaconic acid; Mitochondrion; Peroxisome; Green fluorescent protein; Sorting signal
Funding
- National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
- Costeff Support Group Foundation
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3-Methylglutaconic aciduria type Ill (3-MGCA type III), caused by recessive mutations in the 2-exon gene OPA3, is characterized by early-onset bilateral optic atrophy, later-onset extrapyramidal dysfunction, and increased urinary excretion of 3-methylglutaconic acid and 3-methylglutaric acid. Here we report the identification of a novel third OPA3 coding exon, the apparent product of a segmental duplication event, resulting in two gene transcripts, OPA3A and OPA3B. OPA3A deficiency (as in optic atrophy type 3) causes up-regulation of OPA3B. OPA3 protein function remains unknown, but it contains a putative mitochondrial leader sequence, mitochondrial sorting signal and a peroxisomal sorting signal. Our green fluorescent protein tagged OPA3 expression studies found its localization to be predominantly mitochondrial. These findings thus place the cellular metabolic defect of 3-MGCA type III in the mitochondrion rather than the peroxisome and implicate loss of OPA3A rather than gain of OPA3B in disease etiology. Published by Elsevier Inc.
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