Longevity & AgingAIFM1 Protein Acts as Metabolic Hub by Binding Energy Enzyme AK2A in Mitochondria
Researchers mapped the interaction partners of AIFM1, a mitochondrial protein linked to neurodegeneration and heart disease, identifying adenylate kinase 2A (AK2A) as a key binding partner. Using cryo-EM at near-atomic resolution, they showed AK2A and MIA40 bind the same site on AIFM1's C-terminal domain, stabilizing its active dimer form and boosting its NADH oxidoreductase activity. The AIFM1-AK2A interaction is isoform-specific—only AK2A, not AK2B, binds AIFM1—due to a conserved seven-amino-acid C-terminal sequence unique to AK2A. This interaction appears critical during mitochondrial respiration, with AIFM1 acting as a scaffold that concentrates metabolic enzymes in the intermembrane space to optimize bioenergetic output.
