IBG researchers contribute to international mitochondrial study
IBG researchers contribute to international mitochondrial study
An international study featuring contributions from Dr. Ezgi Karaca and Dr. Ayşe Berçin Barlas of the Izmir Biomedicine and Genome Center (IBG) provides significant insights into the fine-tuned control of cellular energy production. Published in Molecular Cell (IF: 16.6), the research reveals that the mitochondrial proteins apoptosis-inducing factor 1 (AIFM1) and adenylate kinase 2 (AK2) form a specific complex in the presence of NADH, playing a critical role in intracellular energy regulation.
The study employed a multidisciplinary approach, combining cryo-electron microscopy (cryo-EM), chemical cross-linking, and cellular analyses. IBG researchers led the computational structural biology component of the study, mapping the structural changes AIFM1 undergoes upon binding NADH at the atomic level using molecular dynamics simulations. The simulation data also revealed that the C-terminal motif of AK2 binds to AIFM1 via a “seatbelt-like” mechanism. Furthermore, the simulations confirmed that the flexible AK2 binding regions observed in the cryo-EM structures are sensitive to the presence of NADH.
These findings not only shed light on the molecular mechanisms behind mitochondrial energy balance but also represent a significant step toward understanding mitochondrial diseases and developing new therapeutic strategies.
Article link: https://www.sciencedirect.com/science/article/pii/S1097276525005076