Idh3A Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
{{Infobox gene
| symbol = IDH3A
| name = Isocitrate Dehydrogenase 3 Alpha
| chromosome = 7
| locus = 7q32.2
| geneID = 3419
| omim = 147700
| ensembl = ENSG00000168263
| uniprot = P00343
| uniprot_name = IDH3A
| diseases = Retinitis Pigmentosa, Leigh Syndrome, Stroke
| diseases_ref = Lee et al., 2020, Brain
}}
Isocitrate dehydrogenase 3 alpha (IDH3A) is a nuclear-encoded mitochondrial enzyme that catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG) in the tricarboxylic acid (TCA) cycle. Unlike its paralogs IDH1 (cytosolic, NADP+-dependent) and IDH2 (mitochondrial, NADP+-dependent), IDH3A is NAD+-dependent and functions as a heterotetramer composed of α, β, and γ subunits. The IDH3A gene is located on chromosome 7q32.2 and encodes a protein of 413 amino acids. In the brain, IDH3A is expressed primarily in neurons where it plays a critical role in oxidative energy metabolism and ATP production. Mutations in IDH3A are associated with autosomal dominant retinitis pigmentosa, Leigh syndrome, and stroke susceptibility. The enzyme's activity is regulated by adenine nucleotides (ADP activating, ATP inhibiting) and calcium ions, linking its function to cellular energy status and neuronal activity.
Isocitrate dehydrogenase 3 alpha (IDH3A) is a mitochondrial enzyme that catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate in the TCA cycle, using NAD+ as a cofactor. Unlike IDH1 (cytosolic) and IDH2 (mitochondrial NADP+-dependent), IDH3A is NAD+-dependent.
IDH3A is one of three subunits (α, β, γ) that form the active IDH3 heterotetramer. The enzyme catalyzes: Isocitrate + NAD+ → α-Ketoglutarate + NADH + CO2. This is a rate-limiting step in the TCA cycle.
IDH3A activity is regulated by:
In neurons, IDH3A is crucial for:
IDH3A mutations cause autosomal dominant retinitis pigmentosa. The mutations lead to:
IDH3A deficiency can cause Leigh syndrome, characterized by:
IDH3A activity decreases during cerebral ischemia, contributing to:
IDH3A is expressed in:
The study of Idh3A Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Hamilton J et al.. "Mutant huntingtin does not cross the mitochondrial outer membrane." Human molecular genetics (2020) DOI:10.1093/hmg/ddaa185
Tommasini-Ghelfi S et al.. "Cancer-associated mutation and beyond: The emerging biology of isocitrate dehydrogenases in human disease." Science advances (2019) DOI:10.1126/sciadv.aaw4543