IDH1 and neoplasm: For example, knockdown of Me1, an NADPH regeneration enzyme that primarily localizes in the cytoplasm is shown to trigger an increase in Idh2 expression in mitochondrion in several tumor cell lines.52 In contact-inhibited fibroblasts, a flux from α-KG to citrate via IDH2 in the TCA cycle is enhanced to shuttle NADPH from the mitochondrion to cytosol for redox defense or fatty acid synthesis.53 In our study, we demonstrate that disrupted functions of Fe-S cluster proteins are attributed to redistribution of cytoplasmic and mitochondrial NADPH, which requires a functional IDH/α-KG shuttle.