AUTAC4 is a mitochondria-targeting autophagy-targeting chimera (AUTAC). AUTAC4 downregulates cytosolic proteins and promotes targeted mitochondrial turnover via mitophagy[1].
AUTAC4 induces K63-linked polyubiquitination. Accumulation of K63-linked polyubiquitin required approximately 8 h of incubation[1].AUTAC4 suppresses not only cytochrome c release into the cytosol but also pro-caspase 3 cleavage. The intracellular ATP level after CCCP treatment is also maintained by AUTAC4, suggesting that mitophagy acceleration by AUTAC4 restored energy production by improving mitochondrial quality control. AUTAC4 rescues cells with acute mitochondrial injury by promoting mitophagy[1].With the use of mito-Rosella, AUTAC4 (10 μM) can induce mitophagy in Detroit 532 cells ~24-72 h after treatment[1].
[1]. Daiki Takahashi, et al. AUTACs: Cargo-Specific Degraders Using Selective Autophagy. Mol Cell. 2019 Dec 5;76(5):797-810.e10.