IDH1 mutations in gliomas reduce enzyme activity and induce HIF-1α. IDH1 mutations in gliomas impair the enzyme's ability to bind isocitrate, leading to reduced catalytic activity and increased HIF-1α levels. HIF-1α is a transcription factor that promotes tumor growth under low oxygen conditions. The study shows that IDH1 mutations, particularly R132H, form heterodimers with wild-type IDH1, inhibiting its activity and reducing α-ketoglutarate (α-KG) levels. This reduction in α-KG stabilizes HIF-1α, increasing its levels and activating HIF-1α target genes such as Glut1, VEGF, and PGK1. These findings suggest that IDH1 functions as a tumor suppressor, and its inactivation contributes to tumorigenesis by activating the HIF-1α pathway. The study also highlights that IDH1 mutations in gliomas are associated with increased HIF-1α levels and VEGF expression. The results indicate that drugs mimicking α-KG may be effective in treating gliomas with IDH1 mutations.IDH1 mutations in gliomas reduce enzyme activity and induce HIF-1α. IDH1 mutations in gliomas impair the enzyme's ability to bind isocitrate, leading to reduced catalytic activity and increased HIF-1α levels. HIF-1α is a transcription factor that promotes tumor growth under low oxygen conditions. The study shows that IDH1 mutations, particularly R132H, form heterodimers with wild-type IDH1, inhibiting its activity and reducing α-ketoglutarate (α-KG) levels. This reduction in α-KG stabilizes HIF-1α, increasing its levels and activating HIF-1α target genes such as Glut1, VEGF, and PGK1. These findings suggest that IDH1 functions as a tumor suppressor, and its inactivation contributes to tumorigenesis by activating the HIF-1α pathway. The study also highlights that IDH1 mutations in gliomas are associated with increased HIF-1α levels and VEGF expression. The results indicate that drugs mimicking α-KG may be effective in treating gliomas with IDH1 mutations.