Excess peroxisomes are degraded by autophagic machinery in mammals.
Peroxisomes are degraded by autophagic machinery termed "pexophagy" in yeast; however, whether this is essential for peroxisome degradation in mammals remains unknown. Here we have shown that Atg7, an essential gene for autophagy, plays a pivotal role in the degradation of excess peroxisomes in mammals. Following induction of peroxisomes by a 2-week treatment with phthalate esters in control and Atg7-deficient livers, peroxisomal degradation was monitored within 1 week after discontinuation of phthalate esters. Although most of the excess peroxisomes in the control liver were selectively degraded within 1 week, this rapid removal was exclusively impaired in the mutant liver. Furthermore, morphological analysis revealed that surplus peroxisomes, but not mutant hepatocytes, were surrounded by autophagosomes in the control. Our results indicated that the autophagic machinery is essential for the selective clearance of excess peroxisomes in mammals. This is the first direct evidence for the contribution of autophagic machinery in peroxisomal degradation in mammals.
Iwata
Jun-ichi
J
Department of Biochemistry, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.
Ezaki
Junji
J
Komatsu
Masaaki
M
Yokota
Sadaki
S
Ueno
Takashi
T
Tanida
Isei
I
Chiba
Tomoki
T
Tanaka
Keiji
K
Kominami
Eiki
E
D000818:Animals; D001343:Autophagy; D000071193:Autophagy-Related Protein 7; D004051:Diethylhexyl Phthalate / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000502:physiology; D020675:Peroxisomes / Q000187:drug effects / Q000378:metabolism*
C502661:Atg7 protein, mouse; D008869:Microtubule-Associated Proteins; D004051:Diethylhexyl Phthalate; D000071193:Autophagy-Related Protein 7