The peroxisomal AAA ATPase complex prevents pexophagy and development of peroxisome biogenesis disorders

Autophagy
Kelsey B LawPeter K Kim

Abstract

Peroxisome biogenesis disorders (PBDs) are metabolic disorders caused by the loss of peroxisomes. The majority of PBDs result from mutation in one of 3 genes that encode for the peroxisomal AAA ATPase complex (AAA-complex) required for cycling PEX5 for peroxisomal matrix protein import. Mutations in these genes are thought to result in a defect in peroxisome assembly by preventing the import of matrix proteins. However, we show here that loss of the AAA-complex does not prevent matrix protein import, but instead causes an upregulation of peroxisome degradation by macroautophagy, or pexophagy. The loss of AAA-complex function in cells results in the accumulation of ubiquitinated PEX5 on the peroxisomal membrane that signals pexophagy. Inhibiting autophagy by genetic or pharmacological approaches rescues peroxisome number, protein import and function. Our findings suggest that the peroxisomal AAA-complex is required for peroxisome quality control, whereas its absence results in the selective degradation of the peroxisome. Thus the loss of peroxisomes in PBD patients with mutations in their peroxisomal AAA-complex is a result of increased pexophagy. Our study also provides a framework for the development of novel therapeutic treat...Continue Reading

References

Aug 14, 1999·Biochimica Et Biophysica Acta·E H HettemaH F Tabak
Jan 22, 2005·Molecular Biology of the Cell·Tomohiro Yorimitsu, Daniel J Klionsky
Oct 26, 2005·Cell Death and Differentiation·T Yorimitsu, D J Klionsky
Oct 24, 2006·Biochimica Et Biophysica Acta·Steven J SteinbergHugo W Moser
Feb 17, 2007·The Biochemical Journal·Severine I GharbiMichael D Waterfield
Apr 25, 2007·The Journal of Cell Biology·Harald W PlattaRalf Erdmann
Dec 17, 2008·Proceedings of the National Academy of Sciences of the United States of America·Peter Kijun KimJennifer Lippincott-Schwartz
Mar 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Rui ZhangNancy Braverman
Dec 1, 2010·The Journal of Cell Biology·Seok Min JinRichard J Youle
Dec 30, 2010·Autophagy·Terje Johansen, Trond Lamark
Apr 26, 2011·Methods in Molecular Biology·Venil N Sumantran
May 11, 2011·Traffic·Kanji OkumotoYukio Fujiki
May 31, 2012·The EMBO Journal·Alison M MotleyEwald H Hettema
Aug 9, 2012·Biochimica Et Biophysica Acta·Hans R Waterham, Merel S Ebberink
Sep 12, 2012·Autophagy·Daniel J KlionskyBrian Zuckerbraun
Dec 15, 2012·Journal of Cell Science·Elizabeth DeosaranPeter K Kim
Mar 26, 2013·Acta Pharmacologica Sinica·Ya-ping YangChun-feng Liu
Dec 19, 2013·Biochimie·Harald W PlattaRalf Erdmann
Feb 8, 2014·Molecular Genetics and Metabolism·Shandi HieblerSteven J Steinberg
Mar 5, 2014·The Journal of Cell Biology·Kèvin KnoopsIda J van der Klei
Mar 26, 2014·The Biochemical Journal·Agne KazlauskaiteMiratul M K Muqit
Apr 23, 2014·The Journal of Cell Biology·Lesley A KaneRichard J Youle
May 3, 2014·Nature·Fumika KoyanoNoriyuki Matsuda
May 28, 2014·The Journal of Cell Biology·Koji Okamoto
May 31, 2014·Nature Cell Biology·Alexandra StolzIvan Dikic
Jul 10, 2014·Autophagy·Shun-ichi YamashitaYukio Fujiki
Dec 3, 2014·Cell Metabolism·Katharina M WalterWerner J Kovacs
Jan 23, 2015·Neuron·Alicia M Pickrell, Richard J Youle
Feb 11, 2015·Journal of Molecular Biology·Brooke M GardnerAndreas Martin
Jun 13, 2015·Nature Communications·Susanne CiniawskyPetra Wendler
Jul 15, 2015·Proceedings of the National Academy of Sciences of the United States of America·Neil B BlokThomas Walz
Sep 8, 2015·Nature Cell Biology·Jiangwei ZhangCheryl Lyn Walker
Nov 28, 2015·Biochimica Et Biophysica Acta·Hans R WaterhamRonald J A Wanders

❮ Previous
Next ❯

Citations

Sep 22, 2017·Cell Cycle·Wei Wang, Suresh Subramani
Jul 26, 2017·The Plant Journal : for Cell and Molecular Biology·Kim L GonzalezBonnie Bartel
Dec 12, 2018·EMBO Reports·Jean-Claude FarréSuresh Subramani
Jul 18, 2020·Cells·Jung-Ae Kim
Feb 1, 2019·The Journal of Cell Biology·Victoria RiccioPeter Kijun Kim
Jan 23, 2020·International Journal of Molecular Sciences·Kyla Germain, Peter K Kim
Oct 20, 2018·Frontiers in Cell and Developmental Biology·Nur Mehpare Kocaturk, Devrim Gozuacik
Sep 22, 2018·Histochemistry and Cell Biology·Tanja Eberhart, Werner J Kovacs
Mar 21, 2018·Proceedings of the National Academy of Sciences of the United States of America·Kim L GonzalezBonnie Bartel
Aug 4, 2019·International Journal of Molecular Sciences·Anne Schieferdecker, Petra Wendler
Sep 13, 2020·Experimental & Molecular Medicine·Doo Sin JoDong-Hyung Cho
May 28, 2019·Molecular & Cellular Oncology·Victoria RiccioPeter Kijun Kim
Jul 30, 2019·Autophagy·Elena MarcassaSylvie Urbé
Feb 6, 2020·International Journal of Molecular Sciences·Thomas MastalskiHarald W Platta
Jan 13, 2018·Nature Communications·Brooke M GardnerAndreas Martin
Jan 6, 2021·Neurotoxicity Research·Rachayeeta DebShirisha Nagotu
Nov 22, 2019·Biochimica Et Biophysica Acta. Molecular Cell Research·Markus Kunze
Oct 14, 2020·Trends in Biochemical Sciences·Shanmuga S MahalingamSuresh Subramani
Feb 6, 2021·Biochemical and Biophysical Research Communications·Na Yeon ParkDong-Hyung Cho
Apr 20, 2021·Frontiers in Cell and Developmental Biology·Femke C C KlouwerHans R Waterham
Aug 8, 2021·International Journal of Molecular Sciences·Xiaofan WeiRaekil Park
Sep 24, 2021·The Biochemical Journal·Charles B Trelford, Gianni M Di Guglielmo
Feb 23, 2020·Biochemical and Biophysical Research Communications·Yizhu MuRaekil Park

❮ Previous
Next ❯

Methods Mentioned

BETA
ubiquitination
deubiquitinate
confocal microscopy
transfection

Software Mentioned

Volocity
ImageJ
ZEN

Related Concepts

Related Feeds

Aortic Aneurysm

An aortic aneurysm is the weakening and bulging of the blood vessel wall in the aorta. This causes dilatation of the aorta, which is usually asymptomatic but carries the risk of rupture and hemorrhage. Find the latest research on aortic aneurysms here.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

ATP Synthases

ATP synthases are enzymes located in the inner mitochondrial membrane that catalyze the synthesis of ATP during cellular respiration. Discover the latest research on ATP synthases here.

Aneurysm

Aneurysms are outward distensions or bulges that occurs in a weakened wall of blood vessels. Discover the latest research on aneurysms here.

Autophagy & Aging: Inhibitors

The feed focuses on the role of nuclear export inhibitors and their effect on autophagy and the aging process.