Identification of MOAG-4/SERF as a Regulator of Age-Related Proteotoxicity | Zendy

Tjakko J. van Ham | Zendy; M. Holmberg | Zendy; Annemieke T. van der Goot | Zendy; Eva Teuling | Zendy; Moisés Garcı́a-Arencibia | Zendy; Hyun-Eui Kim | Zendy; Deguo Du | Zendy; Karen L. Thijssen | Zendy; Marit Wiersma | Zendy; Rogier C Burggraaff | Zendy; Petra van Bergeijk | Zendy; Jeroen van Rheenen | Zendy; G. Jerre van Veluw | Zendy; Robert M.W. Hofstra | Zendy; David C. Rubinsztein | Zendy; Ellen A. A. Nollen | Zendy

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Identification of MOAG-4/SERF as a Regulator of Age-Related Proteotoxicity

Author(s) -

Tjakko J. van Ham,

M. Holmberg,

Annemieke T. van der Goot,

Eva Teuling,

Moisés Garcı́a-Arencibia,

Hyun-Eui Kim,

Deguo Du,

Karen L. Thijssen,

Marit Wiersma,

Rogier C Burggraaff,

Petra van Bergeijk,

Jeroen van Rheenen,

G. Jerre van Veluw,

Robert M.W. Hofstra,

David C. Rubinsztein,

Ellen A. A. Nollen

Publication year - 2010

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2010.07.020

Subject(s) - proteotoxicity , biology , protein aggregation , regulator , alpha synuclein , amyloid (mycology) , microbiology and biotechnology , autophagy , caenorhabditis elegans , disease , genetics , parkinson's disease , gene , medicine , apoptosis , botany

Fibrillar protein aggregates are the major pathological hallmark of several incurable, age-related, neurodegenerative disorders. These aggregates typically contain aggregation-prone pathogenic proteins, such as amyloid-beta in Alzheimer's disease and alpha-synuclein in Parkinson's disease. It is, however, poorly understood how these aggregates are formed during cellular aging. Here we identify an evolutionarily highly conserved modifier of aggregation, MOAG-4, as a positive regulator of aggregate formation in C. elegans models for polyglutamine diseases. Inactivation of MOAG-4 suppresses the formation of compact polyglutamine aggregation intermediates that are required for aggregate formation. The role of MOAG-4 in driving aggregation extends to amyloid-beta and alpha-synuclein and is evolutionarily conserved in its human orthologs SERF1A and SERF2. MOAG-4/SERF appears to act independently from HSF-1-induced molecular chaperones, proteasomal degradation, and autophagy. Our results suggest that MOAG-4/SERF regulates age-related proteotoxicity through a previously unexplored pathway, which will open up new avenues for research on age-related, neurodegenerative diseases.

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