Journal
NATURE GENETICS
Volume 40, Issue 10, Pages 1230-1234Publisher
NATURE PORTFOLIO
DOI: 10.1038/ng.223
Keywords
-
Categories
Funding
- NEI NIH HHS [P30 EY014104, R37 EY000169, NIH-EY00169, NIH-EY08683, R01 EY008683, R01 EY000169-36, R01 EY000169, P30-EY014104] Funding Source: Medline
- NHLBI NIH HHS [R01 HL067774, NIH-HL67774] Funding Source: Medline
Ask authors/readers for more resources
Here we describe two families with retinitis pigmentosa, a hereditary neurodegeneration of rod and cone photoreceptors in the retina. Affected family members were homozygous for loss-of-function mutations in IDH3B, encoding the beta-subunit of NAD-specific isocitrate dehydrogenase (NAD-IDH, or IDH3), which is believed to catalyze the oxidation of isocitrate to a-ketoglutarate in the citric acid cycle. Cells from affected individuals had a substantial reduction of NAD-IDH activity, with about a 300-fold increase in the Km for NAD. NADP-specific isocitrate dehydrogenase (NADP-IDH, or IDH2), an enzyme that catalyzes the same reaction, was normal in affected individuals, and they had no health problems associated with the enzyme deficiency except for retinitis pigmentosa. These findings support the hypothesis that mitochondrial NADP-IDH, rather than NAD-IDH, serves as the main catalyst for this reaction in the citric acid cycle outside the retina, and that the retina has a particular requirement for NAD-IDH.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available