Biogenesis pathways, including cytosolic targeting, membrane insertion, and quality control, are depicted (SA, black; TA, light gray; and polytopic, dark gray). Nascent substrates are likely triaged during targeting, with SA proteins targeted through TTC1 and polytopic proteins using NAC. All proteins converge at MTCH1/2 for insertion, with some polytopic proteins depending more heavily on recruitment by TOMM70. Similarly, MARCHF5 handles quality control for substrates of all topologies, with some variation within each type. In the cytosol, quality control processes are more divergent, with TA proteins degraded using UBQLNs and no definitive pathway for other protein types.
