Abstract
The proper production, degradation, folding and activity of proteins, proteostasis, is essential for any cellular function. From single cell organisms to humans, selective pressures have led to the evolution of adaptive programs that ensure proteins are properly produced and disposed of when necessary. Environmental factors such as temperature, nutrient availability, pathogens as well as predators have greatly influenced the development of mechanisms such as the unfolded protein response, endoplasmic reticulum-associated protein degradation and autophagy, working together in concert to secure cellular proteostasis. In our modern society, the metabolic systems of the human body face the distinct challenge of changed diets, chronic overnutrition and sedentary lifestyles. Obesity and excess white adipose tissue accumulation are linked to a cluster of metabolic diseases and disturbed proteostasis is a common feature. Conversely, processes that promote energy expenditure such as exercise, shivering as well as non-shivering thermogenesis by brown adipose tissue (BAT) and beige adipocytes counteract metabolic dysfunction. Here we review the basic concepts of proteostasis in obesity-linked metabolic diseases and focus on adipocytes, which are critical regulators of mammalian energy metabolism.
Acknowledgments
We thank Gökhan S. Hotamisligil for stimulating discussions and support over the years. A.B. was supported by the Deutsche Forschungsgemeinschaft Sonderforschungsbereich 1123 (B10), and a Deutsches Zentrum für Herz-Kreislauf-Forschung Junior Research Group Grant. S.B.W. was supported by the University of Saskatchewan, the Saskatchewan Health Research Foundation, the Natural Sciences & Engineering Research Council of Canada, and the Canadian Institute of Health Research. We apologize to colleagues whose work we could not cite due to space limitations.
Conflict of interest statement: The authors declare no conflict of interest.
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Articles in the same Issue
- Frontmatter
- Reviews
- Redefining proteostasis transcription factors in organismal stress responses, development, metabolism, and health
- Proteostasis in thermogenesis and obesity
- Research Articles/Short Communications
- Protein Structure and Function
- Citrate synthase desuccinylation by SIRT5 promotes colon cancer cell proliferation and migration
- Membranes, Lipids, Glycobiology
- Core 1 O-N-acetylgalactosamine (O-GalNAc) glycosylation in the human cell nucleus
- Cell Biology and Signaling
- LncRNA ELFN1-AS1 promotes esophageal cancer progression by up-regulating GFPT1 via sponging miR-183-3p
- Vemurafenib downmodulates aggressiveness mediators of colorectal cancer (CRC): Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP), Protein Tyrosine Phosphatase 1B (PTP1B) and Transforming Growth Factor β (TGFβ)
- Osteopontin enhances the migration of lung fibroblasts via upregulation of interleukin-6 through the extracellular signal-regulated kinase (ERK) pathway
- A role of heparan sulphate proteoglycan in the cellular uptake of lipocalins ß-lactoglobulin and allergen Fel d 4
- A progesterone receptor membrane component 1 antagonist induces large vesicles independent of progesterone receptor membrane component 1 expression
Articles in the same Issue
- Frontmatter
- Reviews
- Redefining proteostasis transcription factors in organismal stress responses, development, metabolism, and health
- Proteostasis in thermogenesis and obesity
- Research Articles/Short Communications
- Protein Structure and Function
- Citrate synthase desuccinylation by SIRT5 promotes colon cancer cell proliferation and migration
- Membranes, Lipids, Glycobiology
- Core 1 O-N-acetylgalactosamine (O-GalNAc) glycosylation in the human cell nucleus
- Cell Biology and Signaling
- LncRNA ELFN1-AS1 promotes esophageal cancer progression by up-regulating GFPT1 via sponging miR-183-3p
- Vemurafenib downmodulates aggressiveness mediators of colorectal cancer (CRC): Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP), Protein Tyrosine Phosphatase 1B (PTP1B) and Transforming Growth Factor β (TGFβ)
- Osteopontin enhances the migration of lung fibroblasts via upregulation of interleukin-6 through the extracellular signal-regulated kinase (ERK) pathway
- A role of heparan sulphate proteoglycan in the cellular uptake of lipocalins ß-lactoglobulin and allergen Fel d 4
- A progesterone receptor membrane component 1 antagonist induces large vesicles independent of progesterone receptor membrane component 1 expression