Selective protein turnover is important for the survival of all organisms. Mycobacterium tuberculosis and related bacteria rely on processive protein degradation pathways in order to survive adverse conditions encountered in their environment or inside the infected host. We investigate large, compartmentalizing degradation complexes and their substrate recruitment mechanisms, including the mycobacterial proteasome and a ubiquitin-like, post-translational protein modification termed pupylation that recruits substrates for proteasomal degradation.