Ubiquilin functions in autophagy and is degraded by chaperone-mediated autophagy

Cara Rothenberg, Deepa Srinivasan, Leann Mah, Susmita Kaushik, Corrine M. Peterhoff, Janet Ugolino, Shengyun Fang, Ana Maria Cuervo, Ralph A. Nixon, Mervyn J. Monteiro

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

Autophagy is the process by which organelles and portions of the cytoplasm are degraded in lysosomes. Several different forms of autophagy are known that are distinguishable chiefly by the mode in which cargo is delivered to the lysosome for degradation. Ubiquilin was recently reported to regulate macroautophagy, the form of autophagy in which cytosolic cargo is packaged in a double-membrane structure or autophagosome that fuses with lysosomes for degradation. We confirm here using different morphological and biochemical procedures that ubiquilin is present in autophagosomes in HeLa cells and in brain and liver tissue of mouse. Coimmunoprecipitation studies indicated that ubiquilin binds the autophagosome marker LC3 in a complex and that reduction of ubiquilin expression reduces autophagosome formation, which correlates with a reduction in maturation of LC3-I to the LC3-II form of the protein. We found that ubiquilin is degraded during both macroautophagy and during chaperone-mediated autophagy (CMA), the latter of which involves the active transport of proteins into lysosomes. We discuss the implication of this degradation in mediating cross-talk between macroautophagy and CMA. Finally, we demonstrate that ubiquilin protects cells against starvation-induced cell death propagated by overexpression of mutant Alzheimer's disease PS2N141I protein and green fluorescent protein (GFP)-huntingtin exon-1 fusion protein containing 74 polyglutamines.

Original languageEnglish (US)
Article numberddq231
Pages (from-to)3219-3232
Number of pages14
JournalHuman Molecular Genetics
Volume19
Issue number16
DOIs
StatePublished - Jun 7 2010

Fingerprint

Autophagy
Lysosomes
Proteins
Active Biological Transport
Starvation
Green Fluorescent Proteins
HeLa Cells
Organelles
Exons
Carrier Proteins
Alzheimer Disease
Cytoplasm
Cell Death
Membranes
Autophagosomes
Liver
Brain

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Rothenberg, C., Srinivasan, D., Mah, L., Kaushik, S., Peterhoff, C. M., Ugolino, J., ... Monteiro, M. J. (2010). Ubiquilin functions in autophagy and is degraded by chaperone-mediated autophagy. Human Molecular Genetics, 19(16), 3219-3232. [ddq231]. https://doi.org/10.1093/hmg/ddq231

Ubiquilin functions in autophagy and is degraded by chaperone-mediated autophagy. / Rothenberg, Cara; Srinivasan, Deepa; Mah, Leann; Kaushik, Susmita; Peterhoff, Corrine M.; Ugolino, Janet; Fang, Shengyun; Cuervo, Ana Maria; Nixon, Ralph A.; Monteiro, Mervyn J.

In: Human Molecular Genetics, Vol. 19, No. 16, ddq231, 07.06.2010, p. 3219-3232.

Research output: Contribution to journalArticle

Rothenberg, C, Srinivasan, D, Mah, L, Kaushik, S, Peterhoff, CM, Ugolino, J, Fang, S, Cuervo, AM, Nixon, RA & Monteiro, MJ 2010, 'Ubiquilin functions in autophagy and is degraded by chaperone-mediated autophagy', Human Molecular Genetics, vol. 19, no. 16, ddq231, pp. 3219-3232. https://doi.org/10.1093/hmg/ddq231
Rothenberg C, Srinivasan D, Mah L, Kaushik S, Peterhoff CM, Ugolino J et al. Ubiquilin functions in autophagy and is degraded by chaperone-mediated autophagy. Human Molecular Genetics. 2010 Jun 7;19(16):3219-3232. ddq231. https://doi.org/10.1093/hmg/ddq231
Rothenberg, Cara ; Srinivasan, Deepa ; Mah, Leann ; Kaushik, Susmita ; Peterhoff, Corrine M. ; Ugolino, Janet ; Fang, Shengyun ; Cuervo, Ana Maria ; Nixon, Ralph A. ; Monteiro, Mervyn J. / Ubiquilin functions in autophagy and is degraded by chaperone-mediated autophagy. In: Human Molecular Genetics. 2010 ; Vol. 19, No. 16. pp. 3219-3232.
@article{fe7d28f2effd40698fd10c4a4873d054,
title = "Ubiquilin functions in autophagy and is degraded by chaperone-mediated autophagy",
abstract = "Autophagy is the process by which organelles and portions of the cytoplasm are degraded in lysosomes. Several different forms of autophagy are known that are distinguishable chiefly by the mode in which cargo is delivered to the lysosome for degradation. Ubiquilin was recently reported to regulate macroautophagy, the form of autophagy in which cytosolic cargo is packaged in a double-membrane structure or autophagosome that fuses with lysosomes for degradation. We confirm here using different morphological and biochemical procedures that ubiquilin is present in autophagosomes in HeLa cells and in brain and liver tissue of mouse. Coimmunoprecipitation studies indicated that ubiquilin binds the autophagosome marker LC3 in a complex and that reduction of ubiquilin expression reduces autophagosome formation, which correlates with a reduction in maturation of LC3-I to the LC3-II form of the protein. We found that ubiquilin is degraded during both macroautophagy and during chaperone-mediated autophagy (CMA), the latter of which involves the active transport of proteins into lysosomes. We discuss the implication of this degradation in mediating cross-talk between macroautophagy and CMA. Finally, we demonstrate that ubiquilin protects cells against starvation-induced cell death propagated by overexpression of mutant Alzheimer's disease PS2N141I protein and green fluorescent protein (GFP)-huntingtin exon-1 fusion protein containing 74 polyglutamines.",
author = "Cara Rothenberg and Deepa Srinivasan and Leann Mah and Susmita Kaushik and Peterhoff, {Corrine M.} and Janet Ugolino and Shengyun Fang and Cuervo, {Ana Maria} and Nixon, {Ralph A.} and Monteiro, {Mervyn J.}",
year = "2010",
month = "6",
day = "7",
doi = "10.1093/hmg/ddq231",
language = "English (US)",
volume = "19",
pages = "3219--3232",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "16",

}

TY - JOUR

T1 - Ubiquilin functions in autophagy and is degraded by chaperone-mediated autophagy

AU - Rothenberg, Cara

AU - Srinivasan, Deepa

AU - Mah, Leann

AU - Kaushik, Susmita

AU - Peterhoff, Corrine M.

AU - Ugolino, Janet

AU - Fang, Shengyun

AU - Cuervo, Ana Maria

AU - Nixon, Ralph A.

AU - Monteiro, Mervyn J.

PY - 2010/6/7

Y1 - 2010/6/7

N2 - Autophagy is the process by which organelles and portions of the cytoplasm are degraded in lysosomes. Several different forms of autophagy are known that are distinguishable chiefly by the mode in which cargo is delivered to the lysosome for degradation. Ubiquilin was recently reported to regulate macroautophagy, the form of autophagy in which cytosolic cargo is packaged in a double-membrane structure or autophagosome that fuses with lysosomes for degradation. We confirm here using different morphological and biochemical procedures that ubiquilin is present in autophagosomes in HeLa cells and in brain and liver tissue of mouse. Coimmunoprecipitation studies indicated that ubiquilin binds the autophagosome marker LC3 in a complex and that reduction of ubiquilin expression reduces autophagosome formation, which correlates with a reduction in maturation of LC3-I to the LC3-II form of the protein. We found that ubiquilin is degraded during both macroautophagy and during chaperone-mediated autophagy (CMA), the latter of which involves the active transport of proteins into lysosomes. We discuss the implication of this degradation in mediating cross-talk between macroautophagy and CMA. Finally, we demonstrate that ubiquilin protects cells against starvation-induced cell death propagated by overexpression of mutant Alzheimer's disease PS2N141I protein and green fluorescent protein (GFP)-huntingtin exon-1 fusion protein containing 74 polyglutamines.

AB - Autophagy is the process by which organelles and portions of the cytoplasm are degraded in lysosomes. Several different forms of autophagy are known that are distinguishable chiefly by the mode in which cargo is delivered to the lysosome for degradation. Ubiquilin was recently reported to regulate macroautophagy, the form of autophagy in which cytosolic cargo is packaged in a double-membrane structure or autophagosome that fuses with lysosomes for degradation. We confirm here using different morphological and biochemical procedures that ubiquilin is present in autophagosomes in HeLa cells and in brain and liver tissue of mouse. Coimmunoprecipitation studies indicated that ubiquilin binds the autophagosome marker LC3 in a complex and that reduction of ubiquilin expression reduces autophagosome formation, which correlates with a reduction in maturation of LC3-I to the LC3-II form of the protein. We found that ubiquilin is degraded during both macroautophagy and during chaperone-mediated autophagy (CMA), the latter of which involves the active transport of proteins into lysosomes. We discuss the implication of this degradation in mediating cross-talk between macroautophagy and CMA. Finally, we demonstrate that ubiquilin protects cells against starvation-induced cell death propagated by overexpression of mutant Alzheimer's disease PS2N141I protein and green fluorescent protein (GFP)-huntingtin exon-1 fusion protein containing 74 polyglutamines.

UR - http://www.scopus.com/inward/record.url?scp=77955023765&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955023765&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddq231

DO - 10.1093/hmg/ddq231

M3 - Article

VL - 19

SP - 3219

EP - 3232

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 16

M1 - ddq231

ER -