Fig. 1.

Surveillance of mitochondrial protein import in yeast. Yeast cells developed steady-state quality control mechanisms as well as transcriptional stress responses to safeguard the mitochondrial protein import process and sustain proteostasis. A The mitochondrial translocation-associated degradation (mitoTAD) mechanism constitutively monitors the TOM complex under homeostatic conditions. Ubx2 recruits the Cdc48–Ufd1–Npl4 protein complex to the import pore to remove arrested precursors and deliver them to the proteasome for degradation. B Severe import defects require further mechanisms to prevent collapse of the import process. The mitochondrial compromised protein import response (mitoCPR), a process active at the site of the translocase, entails the Pdr3-dependent expression of Cis1, an adapter protein that recruits the AAA-ATPase Msp1 to the TOM complex for the extraction of arrested precursors from the translocase and subsequent proteasomal degradation. Grave import defects also result in mitochondrial precursor overaccumulation stress (mPOS) in the cytosol. As a response, yeast cells activate a program called unfolded protein response activated by the mistargeting of proteins (UPRam). The transcription factors Hsf1 and Rpn4 mediate the reduction of cytosolic protein synthesis, expression of heat shock proteins and an increased proteasomal degradation of proteins. MitoCPR and UPRam are interconnected through Rpn4, which promotes UPRam, as well as initiation of mitoCPR to eliminate arrested precursors form the mitochondrial import channel