Figure 5.

Quality control of blocked translocases. (A) In mitochondrial protein translocation-associated degradation (mitoTAD), Ubx2 with Doa1 recruits Cdc48 that transfers clogged precursor protein to proteasomal degradation. (B) In mitochondrial compromised protein import response (mitoCPR), import failure stress triggers the expression of Cis1 through transcription factor Pdr3. Cis1 localizes to the blocked translocases, anchoring the Msp1 AAA ATPase. Msp1 extracts blocked precursor proteins that the proteasome can degrade. (C) Mitochondria associated degradation (MAD) provides quality control to mislocalized or damaged outer membrane proteins by means analogous to translocase unblocking. Proteins are extracted either by Cdc48 (p97 in humans) or by Msp1 (ATAD1 in humans). Extracted proteins are processed by the ubiquitin-proteasome system.