Abstract
Autophagy and the ubiquitin-proteasome system are the two major quality control pathways responsible for cellular homeostasis. As such, they provide protection against age-associated changes and a plethora of human diseases. Ubiquitination is utilized as a degradation signal by both systems, albeit in different ways, to mark cargoes for proteasomal and lysosomal degradation. Both systems intersect and communicate at multiple points to coordinate their actions in proteostasis and organelle homeostasis. This review summarizes molecular details of how proteasome and autophagy pathways are functionally interconnected in cells and indicates common principles and nodes of communication that can be therapeutically exploited.
Keywords:
UPS; aggrephagy; autophagy; chaperone; mitophagy; organelle homeostasis; p62–Keap1–Nrf2; proteasome; proteostasis; ubiquitination; xenophagy.
MeSH terms
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Autophagy / genetics*
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Eukaryotic Cells / cytology
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Eukaryotic Cells / metabolism
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Gene Expression Regulation
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Homeostasis
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Humans
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Kelch-Like ECH-Associated Protein 1 / chemistry
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Kelch-Like ECH-Associated Protein 1 / genetics
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Kelch-Like ECH-Associated Protein 1 / metabolism*
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Mitophagy / genetics
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Molecular Chaperones / genetics
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Molecular Chaperones / metabolism
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NF-E2-Related Factor 2 / chemistry
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NF-E2-Related Factor 2 / genetics
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NF-E2-Related Factor 2 / metabolism*
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Proteasome Endopeptidase Complex / metabolism*
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Protein Conformation
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Proteolysis
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Sequestosome-1 Protein / chemistry
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Sequestosome-1 Protein / genetics
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Sequestosome-1 Protein / metabolism*
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Signal Transduction
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Ubiquitin / genetics
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Ubiquitin / metabolism*
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Ubiquitination
Substances
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KEAP1 protein, human
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Kelch-Like ECH-Associated Protein 1
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Molecular Chaperones
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NF-E2-Related Factor 2
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NFE2L2 protein, human
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SQSTM1 protein, human
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Sequestosome-1 Protein
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Ubiquitin
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Proteasome Endopeptidase Complex