Fig. 6.

Transcriptional regulation of mitophagy. a Under conditions of mitochondrial and endoplasmic reticulum (ER) stress, Parkin expression can be induced by the PERK/ATF4 pathway, and suppressed by the JNK/c-Jun pathway. Further, p53 and Parkin interactions form complex crosstalk. p53 can induce Parkin expression, and Parkin can inhibit p53 expression, forming a negative feedback circuit. In addition, cytosolic p53 can inhibit Parkin translocation to mitochondria. b Nix expression is induced by G(q) signaling via SP1, by hypoxia via HIF1 and p53, and FOXO3. Nix expression can be suppressed via FOXO3 activation of CITED2. Both Nix and FUNDC1 are negatively co-regulated by microRNAs. miR-351 and hsa-miR-125a-5p target Nix, and miR-137 co-targets Nix and FUNDC1. c Bnip3 expression is increased by Ras activity and induced during hypoxia by HIF1. E2F and FOXO3 activate, and NFkB suppresses Bnip3 expression. Black arrows indicate post-translational regulation; green arrows indicate transcriptional activation; red arrows indicate transcriptional repression