Unique Structural Features of the Mitochondrial AAA+ Protease AFG3L2 Reveal the Molecular Basis for Activity in Health and Disease (Molecular Cell)

The AFG3L2 protease maintains protein quality control in mitochondria. Puchades et al. report a cryo-EM structure of AFG3L2 that reveals how structural adaptations are used to pull substrates into a degradation chamber. Neurodegenerative disease-relevant mutations cluster to these unique features and alter the activity and stability of the protease.