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- Title
Inhibition of BRD4 Promotes Pexophagy by Increasing ROS and ATM Activation.
- Authors
Kim, Yong Hwan; Jo, Doo Sin; Park, Na Yeon; Bae, Ji-Eun; Kim, Joon Bum; Lee, Ha Jung; Kim, So Hyun; Kim, Seong Hyun; Lee, Sunwoo; Son, Mikyung; Park, Kyuhee; Jeong, Kwiwan; Yeom, Eunbyul; Cho, Dong-Hyung
- Abstract
Although autophagy regulates the quality and quantity of cellular compartments, the regulatory mechanisms underlying peroxisomal autophagy (pexophagy) remain largely unknown. In this study, we identified several BRD4 inhibitors, including molibresib, a novel pexophagy inducer, via chemical library screening. Treatment with molibresib promotes loss of peroxisomes selectively, but not mitochondria, ER, or Golgi apparatus in HeLa cells. Consistently, depletion of BRD4 expression also induced pexophagy in RPE cells. In addition, the inhibition of BRD4 by molibresib increased autophagic degradation of peroxisome ATG7-dependency. We further found that molibresib produced reactive oxygen species (ROS), which potentiates ATM activation. Inhibition of ROS or ATM suppressed the loss of peroxisomes in molibresib-treated cells. Taken together, our data suggest that inhibition of BRD4 promotes pexophagy by increasing ROS and ATM activation.
- Subjects
AUTOPHAGY; GOLGI apparatus; AUTOMATED teller machines; REACTIVE oxygen species; PEROXISOMES; CHEMICAL libraries; HELA cells
- Publication
Cells (2073-4409), 2022, Vol 11, Issue 18, pN.PAG
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells11182839