AAA+ ATPase chaperone p97/VCP
Peroxisomes
/ metabolism
Valosin Containing Protein
/ metabolism
Humans
Animals
Mice
Membrane Proteins
/ metabolism
Macroautophagy
Autophagy
/ physiology
Membrane Transport Proteins
/ metabolism
HEK293 Cells
Adenosine Triphosphatases
/ metabolism
Molecular Chaperones
/ metabolism
HeLa Cells
Cell Cycle Proteins
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
29 Oct 2024
29 Oct 2024
Historique:
received:
27
06
2023
accepted:
14
10
2024
medline:
30
10
2024
pubmed:
30
10
2024
entrez:
30
10
2024
Statut:
epublish
Résumé
Peroxisomes are organelles that are central to lipid metabolism and chemical detoxification. Despite advances in our understanding of peroxisome biogenesis, the mechanisms maintaining peroxisomal membrane proteins remain to be fully elucidated. We show here that mammalian FAF2/UBXD8, a membrane-associated cofactor of p97/VCP, maintains peroxisomal homeostasis by modulating the turnover of peroxisomal membrane proteins such as PMP70. In FAF2-deficient cells, PMP70 accumulation recruits the autophagy adaptor OPTN (Optineurin) to peroxisomes and promotes their autophagic clearance (pexophagy). Pexophagy is also induced by p97/VCP inhibition. FAF2 functions together with p97/VCP to negatively regulate pexophagy rather than as a factor for peroxisome biogenesis. Our results strongly suggest that p97/VCP
Identifiants
pubmed: 39472561
doi: 10.1038/s41467-024-53558-x
pii: 10.1038/s41467-024-53558-x
doi:
Substances chimiques
Valosin Containing Protein
EC 3.6.4.6
Membrane Proteins
0
Membrane Transport Proteins
0
Adenosine Triphosphatases
EC 3.6.1.-
VCP protein, human
EC 3.6.4.6
Molecular Chaperones
0
OPTN protein, human
0
Cell Cycle Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9347Subventions
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : JP19H05712
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : JP15K19037, JP18K14708, JP21K06161
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : JP18H05500, JP16K18545, JP18K06237
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : JP26116007, JP15K21743, JP17H03675
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : JP26000014, JP19H00997
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP23gm1410004
Informations de copyright
© 2024. The Author(s).
Références
Fujiki, Y., Okumoto, K., Mukai, S., Honsho, M. & Tamura, S. Peroxisome biogenesis in mammalian cells. Front. Physiol. 5, 307 (2014).
pubmed: 25177298
pmcid: 4133648
doi: 10.3389/fphys.2014.00307
Zhang, J. et al. ATM functions at the peroxisome to induce pexophagy in response to ROS. Nat. Cell Biol. 17, 1259–1269 (2015).
pubmed: 26344566
pmcid: 4589490
doi: 10.1038/ncb3230
Fujiki, Y. et al. Recent insights into peroxisome biogenesis and associated diseases. J. Cell Sci. 133, jcs236943 (2020).
pubmed: 32393673
doi: 10.1242/jcs.236943
Sargent, G. et al. PEX2 is the E3 ubiquitin ligase required for pexophagy during starvation. J. Cell Biol. 214, 677–690 (2016).
pubmed: 27597759
pmcid: 5021090
doi: 10.1083/jcb.201511034
Bingol, B. et al. The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy. Nature 510, 370–375 (2014).
pubmed: 24896179
doi: 10.1038/nature13418
Liang, J. R. et al. USP30 deubiquitylates mitochondrial Parkin substrates and restricts apoptotic cell death. EMBO Rep. 16, 618–627 (2015).
pubmed: 25739811
pmcid: 4428036
doi: 10.15252/embr.201439820
Cunningham, C. N. et al. USP30 and parkin homeostatically regulate atypical ubiquitin chains on mitochondria. Nat. Cell Biol. 17, 160–169 (2015).
pubmed: 25621951
doi: 10.1038/ncb3097
Gersch, M. et al. Mechanism and regulation of the Lys6-selective deubiquitinase USP30. Nat. Struct. Mol. Biol. 24, 920–930 (2017).
pubmed: 28945249
pmcid: 5757785
doi: 10.1038/nsmb.3475
Sato, Y. et al. Structural basis for specific cleavage of Lys6-linked polyubiquitin chains by USP30. Nat. Struct. Mol. Biol. 24, 911–919 (2017).
pubmed: 28945247
doi: 10.1038/nsmb.3469
Ordureau, A. et al. Global landscape and dynamics of parkin and USP30-dependent ubiquitylomes in ineurons during mitophagic signaling. Mol. Cell 77, 1124–1142.e1110 (2020).
pubmed: 32142685
pmcid: 7098486
doi: 10.1016/j.molcel.2019.11.013
Stach, L. & Freemont, P. S. The AAA+ ATPase p97, a cellular multitool. Biochem. J. 474, 2953–2976 (2017).
pubmed: 28819009
doi: 10.1042/BCJ20160783
Tanaka, A. et al. Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J. Cell Biol. 191, 1367–1380 (2010).
pubmed: 21173115
pmcid: 3010068
doi: 10.1083/jcb.201007013
Kimura, Y. et al. Different dynamic movements of wild-type and pathogenic VCPs and their cofactors to damaged mitochondria in a Parkin-mediated mitochondrial quality control system. Genes Cells 18, 1131–1143 (2013).
pubmed: 24215292
doi: 10.1111/gtc.12103
Koyano, F. et al. Parkin-mediated ubiquitylation redistributes MITOL/March5 from mitochondria to peroxisomes. EMBO Rep. 20, e47728 (2019).
pubmed: 31602805
pmcid: 6893362
doi: 10.15252/embr.201947728
Araki, K. & Nagata, K. Protein folding and quality control in the ER. Cold Spring Harb. Perspect. Biol. 3, a007526 (2011).
pubmed: 21875985
pmcid: 3220362
doi: 10.1101/cshperspect.a007526
Mueller, B., Klemm, E. J., Spooner, E., Claessen, J. H. & Ploegh, H. L. SEL1L nucleates a protein complex required for dislocation of misfolded glycoproteins. Proc. Natl Acad. Sci. USA 105, 12325–12330 (2008).
pubmed: 18711132
pmcid: 2527910
doi: 10.1073/pnas.0805371105
van den Boom, J. & Meyer, H. VCP/p97-mediated unfolding as a principle in protein homeostasis and signaling. Mol. Cell 69, 182–194 (2018).
pubmed: 29153394
doi: 10.1016/j.molcel.2017.10.028
Raman, M. et al. Systematic proteomics of the VCP-UBXD adaptor network identifies a role for UBXN10 in regulating ciliogenesis. Nat. Cell Biol. 17, 1356–1369 (2015).
pubmed: 26389662
pmcid: 4610257
doi: 10.1038/ncb3238
Olzmann, J. A., Richter, C. M. & Kopito, R. R. Spatial regulation of UBXD8 and p97/VCP controls ATGL-mediated lipid droplet turnover. Proc. Natl Acad. Sci. USA 110, 1345–1350 (2013).
pubmed: 23297223
pmcid: 3557085
doi: 10.1073/pnas.1213738110
Schrul, B. & Kopito, R. R. Peroxin-dependent targeting of a lipid-droplet-destined membrane protein to ER subdomains. Nat. Cell Biol. 18, 740–751 (2016).
pubmed: 27295553
pmcid: 4925261
doi: 10.1038/ncb3373
Wang, C. W. & Lee, S. C. The ubiquitin-like (UBX)-domain-containing protein Ubx2/Ubxd8 regulates lipid droplet homeostasis. J. Cell Sci. 125, 2930–2939 (2012).
pubmed: 22454508
Neuber, O., Jarosch, E., Volkwein, C., Walter, J. & Sommer, T. Ubx2 links the Cdc48 complex to ER-associated protein degradation. Nat. Cell Biol. 7, 993–998 (2005).
pubmed: 16179953
doi: 10.1038/ncb1298
Schuberth, C. & Buchberger, A. Membrane-bound Ubx2 recruits Cdc48 to ubiquitin ligases and their substrates to ensure efficient ER-associated protein degradation. Nat. Cell Biol. 7, 999–1006 (2005).
pubmed: 16179952
doi: 10.1038/ncb1299
Schuberth, C., Richly, H., Rumpf, S. & Buchberger, A. Shp1 and Ubx2 are adaptors of Cdc48 involved in ubiquitin-dependent protein degradation. EMBO Rep. 5, 818–824 (2004).
pubmed: 15258615
pmcid: 1299114
doi: 10.1038/sj.embor.7400203
Mårtensson, C. U. et al. Mitochondrial protein translocation-associated degradation. Nature 569, 679–683 (2019).
pubmed: 31118508
doi: 10.1038/s41586-019-1227-y
Marcassa, E. et al. Dual role of USP30 in controlling basal pexophagy and mitophagy. EMBO Rep. 19, e45595 (2018).
pubmed: 29895712
pmcid: 6030704
doi: 10.15252/embr.201745595
Riccio, V. et al. Deubiquitinating enzyme USP30 maintains basal peroxisome abundance by regulating pexophagy. J. Cell Biol. 218, 798–807 (2019).
pubmed: 30700497
pmcid: 6400567
doi: 10.1083/jcb.201804172
Zheng, J., Cao, Y., Yang, J. & Jiang, H. UBXD8 mediates mitochondria-associated degradation to restrain apoptosis and mitophagy. EMBO Rep. 23, e54859 (2022).
pubmed: 35979733
pmcid: 9535754
doi: 10.15252/embr.202254859
Ganji, R. et al. The p97-UBXD8 complex regulates ER-Mitochondria contact sites by altering membrane lipid saturation and composition. Nat. Commun. 14, 638 (2023).
pubmed: 36746962
pmcid: 9902492
doi: 10.1038/s41467-023-36298-2
Katayama, H., Kogure, T., Mizushima, N., Yoshimori, T. & Miyawaki, A. A sensitive and quantitative technique for detecting autophagic events based on lysosomal delivery. Chem. Biol. 18, 1042–1052 (2011).
pubmed: 21867919
doi: 10.1016/j.chembiol.2011.05.013
Yamashita, S.-I., Abe, K., Tatemichi, Y. & Fujiki, Y. The membrane peroxin PEX3 induces peroxisome-ubiquitination-linked pexophagy. Autophagy 10, 1549–1564 (2014).
pubmed: 25007327
pmcid: 4206534
doi: 10.4161/auto.29329
Yim, W. W., Yamamoto, H. & Mizushima, N. A pulse-chasable reporter processing assay for mammalian autophagic flux with HaloTag. Elife 11. https://doi.org/10.7554/eLife.78923 (2022)
Hosokawa, N. et al. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol. Biol. Cell 20, 1981–1991 (2009).
pubmed: 19211835
pmcid: 2663915
doi: 10.1091/mbc.e08-12-1248
Sirozh, O. et al. Nucleolar stress caused by arginine-rich peptides triggers a ribosomopathy and accelerates aging in mice. Mol. Cell 84, 1527–1540.e1527 (2024).
pubmed: 38521064
doi: 10.1016/j.molcel.2024.02.031
Zheng, J., Chen, X., Liu, Q., Zhong, G. & Zhuang, M. Ubiquitin ligase MARCH5 localizes to peroxisomes to regulate pexophagy. J. Cell Biol. 221. https://doi.org/10.1083/jcb.202103156 (2022)
Honsho, M., Yamashita, S. & Fujiki, Y. Peroxisome homeostasis: mechanisms of division and selective degradation of peroxisomes in mammals. Biochim. Biophys. Acta 1863, 984–991 (2016).
pubmed: 26434997
doi: 10.1016/j.bbamcr.2015.09.032
Liu, Y., Yagita, Y. & Fujiki, Y. Assembly of peroxisomal membrane proteins via the direct Pex19p-Pex3p pathway. Traffic 17, 433–455 (2016).
pubmed: 26777132
doi: 10.1111/tra.12376
Matsuzono, Y. et al. Human PEX19: cDNA cloning by functional complementation, mutation analysis in a patient with Zellweger syndrome, and potential role in peroxisomal membrane assembly. Proc. Natl Acad. Sci. USA 96, 2116–2121 (1999).
pubmed: 10051604
pmcid: 26746
doi: 10.1073/pnas.96.5.2116
Yuan, X. et al. Structure, dynamics and interactions of p47, a major adaptor of the AAA ATPase, p97. EMBO J. 23, 1463–1473 (2004).
pubmed: 15029246
pmcid: 391063
doi: 10.1038/sj.emboj.7600152
Maejima, I. et al. Autophagy sequesters damaged lysosomes to control lysosomal biogenesis and kidney injury. EMBO J. 32, 2336–2347 (2013).
pubmed: 23921551
pmcid: 3770333
doi: 10.1038/emboj.2013.171
Okatsu, K. et al. Phosphorylated ubiquitin chain is the genuine Parkin receptor. J. Cell Biol. 209, 111–128 (2015).
pubmed: 25847540
pmcid: 4395490
doi: 10.1083/jcb.201410050
Kim, H. et al. UAS domain of Ubxd8 and FAF1 polymerizes upon interaction with long-chain unsaturated fatty acids. J. Lipid Res. 54, 2144–2152 (2013).
pubmed: 23720822
pmcid: 3708364
doi: 10.1194/jlr.M037218
Johansen, T. & Lamark, T. Selective autophagy mediated by autophagic adapter proteins. Autophagy 7, 279–296 (2011).
pubmed: 21189453
pmcid: 3060413
doi: 10.4161/auto.7.3.14487
Mizushima, N. & Komatsu, M. Autophagy: renovation of cells and tissues. Cell 147, 728–741 (2011).
pubmed: 22078875
doi: 10.1016/j.cell.2011.10.026
Stolz, A., Ernst, A. & Dikic, I. Cargo recognition and trafficking in selective autophagy. Nat. Cell Biol. 16, 495–501 (2014).
pubmed: 24875736
doi: 10.1038/ncb2979
Zaffagnini, G. & Martens, S. Mechanisms of selective autophagy. J. Mol. Biol. 428, 1714–1724 (2016).
pubmed: 26876603
pmcid: 4871809
doi: 10.1016/j.jmb.2016.02.004
Deosaran, E. et al. NBR1 acts as an autophagy receptor for peroxisomes. J. Cell Sci. 126, 939–952 (2013).
pubmed: 23239026
Okumoto, K., Kametani, Y. & Fujiki, Y. Two proteases, trypsin domain-containing 1 (Tysnd1) and peroxisomal lon protease (PsLon), cooperatively regulate fatty acid β-oxidation in peroxisomal matrix. J. Biol. Chem. 286, 44367–44379 (2011).
pubmed: 22002062
pmcid: 3247999
doi: 10.1074/jbc.M111.285197
Yamashita, A. et al. Depletion of LONP2 unmasks differential requirements for peroxisomal function between cell types and in cholesterol metabolism. Biol. Direct 18, 60 (2023).
pubmed: 37736739
pmcid: 10515011
doi: 10.1186/s13062-023-00416-3
Huybrechts, S. J. et al. Peroxisome dynamics in cultured mammalian cells. Traffic 10, 1722–1733 (2009).
pubmed: 19719477
doi: 10.1111/j.1600-0854.2009.00970.x
Kim, P. K., Hailey, D. W., Mullen, R. T. & Lippincott-Schwartz, J. Ubiquitin signals autophagic degradation of cytosolic proteins and peroxisomes. Proc. Natl Acad. Sci. USA 105, 20567–20574 (2008).
pubmed: 19074260
pmcid: 2602605
doi: 10.1073/pnas.0810611105
Phu, L. et al. Dynamic regulation of mitochondrial import by the ubiquitin system. Mol. Cell 77, 1107–1123 e1110 (2020).
pubmed: 32142684
doi: 10.1016/j.molcel.2020.02.012
Fujisawa, R., Polo Rivera, C. & Labib, K. P. M. Multiple UBX proteins reduce the ubiquitin threshold of the mammalian p97-UFD1-NPL4 unfoldase. Elife 11. https://doi.org/10.7554/eLife.76763 (2022)
Heo, J. M., Ordureau, A., Paulo, J. A., Rinehart, J. & Harper, J. W. The PINK1-PARKIN mitochondrial ubiquitylation pathway drives a program of OPTN/NDP52 recruitment and TBK1 activation to promote mitophagy. Mol. Cell 60, 7–20 (2015).
pubmed: 26365381
pmcid: 4592482
doi: 10.1016/j.molcel.2015.08.016
Lazarou, M. et al. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 524, 309–314 (2015).
pubmed: 26266977
pmcid: 5018156
doi: 10.1038/nature14893
Yamano, K. et al. Critical role of mitochondrial ubiquitination and the OPTN-ATG9A axis in mitophagy. J. Cell Biol. 219, e201912144 (2020).
pubmed: 32556086
pmcid: 7480101
doi: 10.1083/jcb.201912144
Noguchi, M. et al. ATPase activity of p97/valosin-containing protein is regulated by oxidative modification of the evolutionally conserved cysteine 522 residue in Walker A motif. J. Biol. Chem. 280, 41332–41341 (2005).
pubmed: 16234241
doi: 10.1074/jbc.M509700200
Yamano, K. et al. Endosomal Rab cycles regulate Parkin-mediated mitophagy. Elife 7, e31326 (2018).
pubmed: 29360040
pmcid: 5780041
doi: 10.7554/eLife.31326
Manno, A., Noguchi, M., Fukushi, J., Motohashi, Y. & Kakizuka, A. Enhanced ATPase activities as a primary defect of mutant valosin-containing proteins that cause inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia. Genes Cells 15, 911–922 (2010).
pubmed: 20604808
doi: 10.1111/j.1365-2443.2010.01428.x
Kirisako, T. et al. A ubiquitin ligase complex assembles linear polyubiquitin chains. EMBO J. 25, 4877–4887 (2006).
pubmed: 17006537
pmcid: 1618115
doi: 10.1038/sj.emboj.7601360
Sato, Y. et al. Structural basis for specific cleavage of Lys 63-linked polyubiquitin chains. Nature 455, 358–362 (2008).
pubmed: 18758443
doi: 10.1038/nature07254