The research titled " NADP+-IDH Mutations Promote Hypersuccinylation that Impairs Mitochondria Respiration and Induces Apoptosis Resistance" was published in "Molecular Cell" on November 19, 2015. This study reveals that mutations in NADP+-dependent isocitrate dehydrogenase (IDH) lead to the accumulation of R-2-hydroxyglutarate (R-2HG), which induces hypersuccinylation, impairs mitochondrial respiration, and promotes apoptosis resistance. The key innovation lies in elucidating the direct link between R-2HG accumulation and mitochondrial dysfunction through hypersuccinylation, highlighting a novel mechanism by which IDH mutations drive tumorigenesis. The study also demonstrates that relieving hypersuccinylation can restore mitochondrial functions and inhibit the oncogenic growth of IDH-mutant cells, suggesting potential therapeutic strategies for cancers associated with IDH mutations.
https://www.cell.com/molecular-cell/fulltext/S1097-2765(15)00808-4?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1097276515008084%3Fshowall%3Dtrue
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