2,2′-dipyridyl induces pexophagy

• Published in: Biochemical and biophysical research communications Vol. 469; no. 4; pp. 941 - 947
• Main Authors: Jin, AiLin, Lee, Joon No, Kim, Min Soo, Kwak, SeongAe, Kim, Se-Jin, Song, Kyung, Choe, Seong-Kyu, Park, Raekil
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.01.2016
• Subjects: 2,2'-Dipyridyl - administration & dosage; 2,2′-dipyridyl; Autophagy; Autophagy - drug effects; Autophagy - physiology; Cell Line; Dose-Response Relationship, Drug; Humans; Iron Chelating Agents - administration & dosage; Iron chelation; Peroxisome dynamics; Peroxisomes - drug effects; Peroxisomes - metabolism; Pexophagy; Retinal Pigment Epithelium - cytology; Retinal Pigment Epithelium - drug effects; Retinal Pigment Epithelium - metabolism; 2,2′-dipyridyl; Iron chelation; Pexophagy; Autophagy; Peroxisome dynamics
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2015.12.098

Pexophagy is the selective degradation of peroxisomes for maintaining peroxisome homeostasis within cells. Peroxisome dynamics and pexophagy are important events required to maintain the quality control of peroxisomes, thereby preventing peroxisome-associated diseases. To identify novel pexophagy modulators, we developed a cell-based screening system and selected 2,2′-dipyridyl (2,2-DP) as a candidate molecule. 2,2-DP treatment induced peroxisome degradation as evidenced by an increased number of low-pH autolysosomes originating from peroxisomes and a decrease in the expression of peroxisomal proteins such as catalase, Pex14, and PMP70. The phenotype was defined as pexophagy, because 2,2-DP induced autophagy and inhibition of autophagy significantly reduced the degree of peroxisome degradation. Mechanistically, 2,2-DP-dependent pexophagy seemed to be mediated by iron chelation, since another iron chelator displayed a similar effect on pexophagy, but a copper chelator did not. Notably, iron replenishment prevented 2,2-DP-mediated pexophagy. Taken together, our results suggest that 2,2-DP treatment disrupts peroxisome dynamics and promotes pexophagy through iron depletion. •2,2-DP treatment enhances pexophagy.•2,2-DP treatment increases pexophagy through autophagy.•Autophagy inhibition blocks 2,2-DP-induced pexophagy.•Iron repletion blocks 2,2-DP-induced pexophagy.