Figure 9.

Interplay between ER stress, mitochondrial stress and parkin. ER stress can induce mitochondrial damage, such as alterations in mitochondrial morphology and bioenergetics. Conversely, mitochondrial stress can induce ER stress, reflected by the induction of the unfolded protein response (UPR). Parkin is transcriptionally upregulated in response to both mitochondrial and ER stress by ATF4, a transcription factor of the UPR. The stress-induced transcriptional upregulation of parkin is antagonized by c-Jun, which is activated by the JNK pathway. Increased expression of parkin under stress conditions protects cells from stress-induced cell death, explaining the high vulnerability of parkin-deficient cells to cellular stress