Idh3a, encoding the α subunit of isocitrate dehydrogenase 3 (IDH3), is a key enzyme in the tricarboxylic acid (TCA) cycle. IDH3 is responsible for generating NADH from isocitrate, which is used in mitochondria for ATP production. The TCA cycle is fundamental for cellular metabolism, providing energy and intermediates for various biosynthetic pathways [1].

Mouse models have been crucial in understanding Idh3a's role. Homozygous knockout of Idh3a leads to early embryonic lethality, indicating its essential role in early development. In mice with a late-onset retinal degeneration model, carrying an ENU-induced mutation (E229K) in Idh3a, homozygous mutants show signs of retinal stress as early as 3 months. Idh3a-/E229K compound heterozygous mutants have a more severe retinal degeneration. Analysis of mutant cell lines reveals a reduction in mitochondrial maximal respiration and reserve capacity levels in both Idh3aE229K/E229K and Idh3a-/E229K cells, suggesting that reduced mitochondrial function due to Idh3a mutations contributes to the retinal degeneration phenotype [1].

In conclusion, Idh3a is essential for normal mitochondrial function and energy production through its role in the TCA cycle. Mouse models, especially those with Idh3a knockout or specific mutations, have been instrumental in highlighting its significance in retinal health. Mutations in Idh3a can lead to reduced mitochondrial function and subsequent retinal degeneration, providing insights into potential mechanisms underlying certain retinal diseases [1].