Fig. 3.

Model of the mitochondrial unfolded protein response (UPR^mt) in C. elegans. Proteotoxic stress triggers a response of ClpXP, whose proteolytic activity is required to transmit the signal to the cytoplasm presumably via peptide translocation by HAF-1. Here, the transcription factors, UBL-5 and DVE-1, which form a complex, and ZC376.7 redistribute to the nucleus. DVE-1 binds to the promoter region of the mitochondrial chaperone genes, hsp-6 and hsp-60. The expression of ubl-5 is also up-regulated and probably acts as a feed-forward regulation to enhance the signal. This activation of the UPR^mt results in an accumulation of HSP-6 (mt Hsp70) and HSP-60 (mt chaperonin) in the mitochondria. RHEB is thought to act as a suppressor of the UPR^mt, probably with cessation of the stress conditions. Open questions of the regulation of the UPR^mt are indicated with question marks and are further discussed in the text.