Fig. 1: Structure, molecular functions, and physiological roles of NDPK-D/NME4 | Laboratory Investigation

Fig. 1: Structure, molecular functions, and physiological roles of NDPK-D/NME4

From: The mitochondrial nucleoside diphosphate kinase (NDPK-D/NME4), a moonlighting protein for cell homeostasis

Fig. 1

The hexameric structure (PDB 1EHW, monomer backbones in different colors, transparent van der Waals surface in gray) indicating one representative NDP kinase active site (red, phosphotransfer function through phosphorylation of histidine 151) and one basic amino acid triad capable of binding anionic phospholipids, including cardiolipin (blue, phospholipid transfer function). These sites define the two molecular functions of NME4: (i) NTP and ADP generation from mitochondrial ATP and NDPs, and (ii) intermembrane transfer of cardiolipin and other anionic phospholipids by simultaneously binding inner and outer mitochondrial membrane. Via the former function, NME4 in the intermembrane space provides GTP to dynamin-related GTPase OPA1 for mitochondrial dynamics and structure, and ADP to sustain oxidative phosphorylation and mitochondrial respiration, while NME4 in the matrix mainly provides building blocks for mtDNA and RNA synthesis, using ATP but also GTP generated in the Krebs cycle. Via its phospholipid transfer function, NME4 in the intermembrane space facilitates CL transfer to the mitochondrial surface as a pro-mitophagic or pro-apoptotic trigger, and may participate in phospholipid biosynthetic pathways between ER and mitochondria. (Figure modified from Schlattner et al. [72])

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