Highlights d Numerous SARS-CoV-2 proteins synergize to suppress immune sensing and signaling d Nsp14 targets IFNAR1 for lysosomal degradation d ORF3a and ORF7a block autophagy by different mechanisms d Synergistic treatment with IFN-g and -l1 is highly effective against SARS-CoV-2

Highlights d Proximity labeling of proteins shows connectivity of mitochondrial gene expression d Interactors at the mRNA channel entrance and exit support translation initiation d Polypeptide tunnel exit serves as a platform to organize OXPHOS assembly factors d Synthesis of Cox1 is directly coupled to co-factor acquisition and early assembly

Highlights d Translational feedback regulation in mitochondria involves a molecular rheostat d Alternate binding of two translational activators to the ribosomal tunnel exit d Ribosomal binding of Cbs1 sequesters COB mRNA to repress translation d Cbp3-Cbp6 liberated during assembly replaces Cbs1 for translational activation