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Crosstalk of proteasomes and autophagy in RPE cells
Author(s) -
KAARNIRANTA K
Publication year - 2013
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2013.2272.x
Subject(s) - autophagy , microbiology and biotechnology , lipofuscin , sequestosome 1 , proteasome , protein aggregation , proteostasis , proteolysis , crosstalk , ubiquitin , chemistry , vacuole , bag3 , lysosome , cytoplasm , biology , biochemistry , apoptosis , enzyme , physics , gene , optics
The pathogenesis of AMD involves impaired protein degradation in RPE cells. The ubiquitin‐proteasome pathway and the lysosomal pathway including autophagy are the major proteolytic systems in eukaryotic cells. Prior to proteolysis, heat shock proteins (HSPs) attempt to refold stress‐induced misfolded proteins and thus prevent the accumulation of cytoplasmic protein aggregates. Recently, p62/sequestosome 1 has been shown to be a key player linking the proteasomal and lysosomal clearance systems.The aging characteristics of the RPE involve lysosomal accumulation of lipofuscin and extracellular protein aggregates drusens. Molecular mechanisms behind protein aggregations are weakly understood. There is intriguing evidence suggesting that p62, together with autophagy, seems to have a role in the pathology of different degenerative diseases. In ARPE‐19 cells proteasomal inhibition caused accumulation of p62 bound irreversibly to perinuclear protein aggregates. The addition of the AMPK activator AICAR was pro‐survival and promoted cleansing by autophagy of the former complex. Human AMD donor samples showed strong p62 accumulation in the drusen rich macula revealing impaired autophagy flux.