Ubiquitination and Selective Autophagy

Overview

Journal Cell Death Differ

Specialty Cell Biology

Date 2012 Jun 23

PMID 22722335

Citations 378

Authors

S Shaid

C H Brandts

H Serve

I Dikic

Affiliations

Soon will be listed here.

Abstract

Ubiquitination has long been recognised as a key determinator of protein fate by tagging proteins for proteasomal degradation. Most recently, the ability of conjugated ubiquitin chains to confer selectivity to autophagy was demonstrated. Although autophagy was first believed to be a bulk, non-selective 'self-eating' degradative process, the molecular mechanisms of selectivity are now starting to emerge. With the discovery of autophagy receptors - which bind both ubiquitinated substrates and autophagy specific light chain 3 (LC3) modifier on the inner sheath of autophagosomes - a new pathway of selective autophagy is being unravelled. In this review, we focus on the special role of ubiquitin signals and selective autophagy receptors in sorting a variety of autophagic cargos.

Citing Articles

LRSAM1 mediated the degradation of intracellular Vibrio through the ubiquitination-autophagy-lysosome pathway in oyster.

Yang W, Sun J, Guo Q, Wang W, Leng J, Wang L Cell Commun Signal. 2025; 23(1):110.

PMID: 40001133 PMC: 11863841. DOI: 10.1186/s12964-025-02111-4.

NEMO Family of Proteins as Polyubiquitin Receptors: Illustrating Non-Degradative Polyubiquitination's Roles in Health and Disease.

Wu C Cells. 2025; 14(4).

PMID: 39996775 PMC: 11854354. DOI: 10.3390/cells14040304.

Quercetin alleviates LPS/iE-DAP-induced liver injury by suppressing ferroptosis via regulating ferritinophagy and intracellular iron efflux.

Zhang H, Shi H, Li X, Zhou S, Song X, Ma N Redox Biol. 2025; 81:103557.

PMID: 39986118 PMC: 11904602. DOI: 10.1016/j.redox.2025.103557.

Targeting intracellular autophagic process for the treatment of post-stroke ischemia/reperfusion injury.

Hu J, Hu Z, Xia J, Chen Y, Cordato D, Cheng Q Animal Model Exp Med. 2025; 8(3):389-404.

PMID: 39908171 PMC: 11904106. DOI: 10.1002/ame2.12528.

VANGL2 alleviates inflammatory bowel disease by recruiting the ubiquitin ligase MARCH8 to limit NLRP3 inflammasome activation through OPTN-mediated selective autophagy.

Jiang H, Xie Y, Hu Z, Lu J, Zhang J, Li H PLoS Biol. 2025; 23(2):e3002961.

PMID: 39899477 PMC: 11790156. DOI: 10.1371/journal.pbio.3002961.

References

Pohl C, Jentsch S . Midbody ring disposal by autophagy is a post-abscission event of cytokinesis. Nat Cell Biol. 2008; 11(1):65-70. DOI: 10.1038/ncb1813. View

Strnad P, Zatloukal K, Stumptner C, Kulaksiz H, Denk H . Mallory-Denk-bodies: lessons from keratin-containing hepatic inclusion bodies. Biochim Biophys Acta. 2008; 1782(12):764-74. DOI: 10.1016/j.bbadis.2008.08.008. View

Ikeda F, Dikic I . Atypical ubiquitin chains: new molecular signals. 'Protein Modifications: Beyond the Usual Suspects' review series. EMBO Rep. 2008; 9(6):536-42. PMC: 2427391. DOI: 10.1038/embor.2008.93. View

Kopito R . Aggresomes, inclusion bodies and protein aggregation. Trends Cell Biol. 2000; 10(12):524-30. DOI: 10.1016/s0962-8924(00)01852-3. View

Scherz-Shouval R, Shvets E, Fass E, Shorer H, Gil L, Elazar Z . Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J. 2007; 26(7):1749-60. PMC: 1847657. DOI: 10.1038/sj.emboj.7601623. View

Xu P, Duong D, Seyfried N, Cheng D, Xie Y, Robert J . Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation. Cell. 2009; 137(1):133-45. PMC: 2668214. DOI: 10.1016/j.cell.2009.01.041. View

Kabeya Y, Mizushima N, Yamamoto A, Oshitani-Okamoto S, Ohsumi Y, Yoshimori T . LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation. J Cell Sci. 2004; 117(Pt 13):2805-12. DOI: 10.1242/jcs.01131. View

Paz Y, Elazar Z, Fass D . Structure of GATE-16, membrane transport modulator and mammalian ortholog of autophagocytosis factor Aut7p. J Biol Chem. 2000; 275(33):25445-50. DOI: 10.1074/jbc.C000307200. View

Kraft C, Deplazes A, Sohrmann M, Peter M . Mature ribosomes are selectively degraded upon starvation by an autophagy pathway requiring the Ubp3p/Bre5p ubiquitin protease. Nat Cell Biol. 2008; 10(5):602-10. DOI: 10.1038/ncb1723. View

10.

Kirkin V, Lamark T, Sou Y, Bjorkoy G, Nunn J, Bruun J . A role for NBR1 in autophagosomal degradation of ubiquitinated substrates. Mol Cell. 2009; 33(4):505-16. DOI: 10.1016/j.molcel.2009.01.020. View

11.

Waters S, Marchbank K, Solomon E, Whitehouse C . Autophagic receptors Nbr1 and p62 coregulate skeletal remodeling. Autophagy. 2010; 6(7):981-3. DOI: 10.4161/auto.6.7.13155. View

12.

Gegg M, Cooper J, Chau K, Rojo M, Schapira A, Taanman J . Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy. Hum Mol Genet. 2010; 19(24):4861-70. PMC: 3583518. DOI: 10.1093/hmg/ddq419. View

13.

Kim P, Hailey D, Mullen R, Lippincott-Schwartz J . Ubiquitin signals autophagic degradation of cytosolic proteins and peroxisomes. Proc Natl Acad Sci U S A. 2008; 105(52):20567-74. PMC: 2602605. DOI: 10.1073/pnas.0810611105. View

14.

DAgostino C, Nogalska A, Cacciottolo M, Engel W, Askanas V . Abnormalities of NBR1, a novel autophagy-associated protein, in muscle fibers of sporadic inclusion-body myositis. Acta Neuropathol. 2011; 122(5):627-36. DOI: 10.1007/s00401-011-0874-3. View

15.

Matsuda N, Sato S, Shiba K, Okatsu K, Saisho K, Gautier C . PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol. 2010; 189(2):211-21. PMC: 2856912. DOI: 10.1083/jcb.200910140. View

16.

Ogawa M, Yoshikawa Y, Kobayashi T, Mimuro H, Fukumatsu M, Kiga K . A Tecpr1-dependent selective autophagy pathway targets bacterial pathogens. Cell Host Microbe. 2011; 9(5):376-89. DOI: 10.1016/j.chom.2011.04.010. View

17.

Xie Z, Nair U, Klionsky D . Atg8 controls phagophore expansion during autophagosome formation. Mol Biol Cell. 2008; 19(8):3290-8. PMC: 2488302. DOI: 10.1091/mbc.e07-12-1292. View

18.

Kettern N, Dreiseidler M, Tawo R, Hohfeld J . Chaperone-assisted degradation: multiple paths to destruction. Biol Chem. 2010; 391(5):481-9. DOI: 10.1515/BC.2010.058. View

19.

Ohsumi Y, Mizushima N . Two ubiquitin-like conjugation systems essential for autophagy. Semin Cell Dev Biol. 2004; 15(2):231-6. DOI: 10.1016/j.semcdb.2003.12.004. View

20.

Korolchuk V, Mansilla A, Menzies F, Rubinsztein D . Autophagy inhibition compromises degradation of ubiquitin-proteasome pathway substrates. Mol Cell. 2009; 33(4):517-27. PMC: 2669153. DOI: 10.1016/j.molcel.2009.01.021. View