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Open AccessFeature PaperReview

Control of Protein Homeostasis in the Early Secretory Pathway: Current Status and Challenges

by Daria Sicari 1,2,*, Aeid Igbaria 1,2 and Eric Chevet 1,2,*
Proteostasis & Cancer Team INSERM U1242 « Chemistry, Oncogenesis Stress Signaling », Université de Rennes, CEDEX, 35042 Rennes, France
Centre de Lutte contre le Cancer Eugène Marquis, CEDEX, 35042 Rennes, France
Authors to whom correspondence should be addressed.
Cells 2019, 8(11), 1347;
Received: 25 September 2019 / Revised: 21 October 2019 / Accepted: 23 October 2019 / Published: 29 October 2019
(This article belongs to the Special Issue Membrane Traffic in Health and Disease)
Discrimination between properly folded proteins and those that do not reach this state is necessary for cells to achieve functionality. Eukaryotic cells have evolved several mechanisms to ensure secretory protein quality control, which allows efficiency and fidelity in protein production. Among the actors involved in such process, both endoplasmic reticulum (ER) and the Golgi complex play prominent roles in protein synthesis, biogenesis and secretion. ER and Golgi functions ensure that only properly folded proteins are allowed to flow through the secretory pathway while improperly folded proteins have to be eliminated to not impinge on cellular functions. Thus, complex quality control and degradation machineries are crucial to prevent the toxic accumulation of improperly folded proteins. However, in some instances, improperly folded proteins can escape the quality control systems thereby contributing to several human diseases. Herein, we summarize how the early secretory pathways copes with the accumulation of improperly folded proteins, and how insufficient handling can cause the development of several human diseases. Finally, we detail the genetic and pharmacologic approaches that could be used as potential therapeutic tools to treat these diseases. View Full-Text
Keywords: ER stress; Golgi stress; ERAD; EGAD; protein quality control ER stress; Golgi stress; ERAD; EGAD; protein quality control
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Sicari, D.; Igbaria, A.; Chevet, E. Control of Protein Homeostasis in the Early Secretory Pathway: Current Status and Challenges. Cells 2019, 8, 1347.

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