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Dynamic droplets: the role of cytoplasmic inclusions in stress, function, and disease

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Abstract

Neurodegenerative diseases and other proteinopathies constitute a class of several dozen illnesses etiologically linked to pathological protein misfolding and aggregation. Because of this strong association with disease pathology, cell death, and aging, accumulation of proteins in aggregates or aggregation-associated structures (inclusions) has come to be regarded by many as a deleterious process, to be avoided if possible. Recent work has led us to see inclusion structures and disordered aggregate-like protein mixtures (which we call dynamic droplets) in a new light: not necessarily as a result of a pathological breakdown of cellular order, but as an elaborate cellular architecture regulating function and stress response. In this review, we discuss what is currently known about the role of inclusion structures in cellular homeostasis, stress response, toxicity, and disease. We will focus on possible mechanisms of aggregate toxicity, in contrast to the homeostatic function of several inclusion structures.

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Acknowledgments

We tried to cite all primary literature pertaining to inclusions and inclusion-like structures. We apologize to any colleagues if we unintentionally missed their studies. We thank Mark Kaganovich, Jeremy England, Richard Gardner, Ehud Cohen, and members of the Kaganovich lab for discussion and feedback on the manuscript. This work was supported by the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC-StG2013 337713 DarkSide starting grant, as well as an Israel Science Foundation Grant ISF 843/11; a German Israel Foundation Grant GIFI-1201-242.13/2012; an Israel Health Ministry grant under the framework of E-Rare-2, a Niedersachsen-Israel Research Program grant, and a grant from the American Federation for Aging Research.

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  1. Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, 91904, Israel

    Triana Amen & Daniel Kaganovich

  2. Alexander Grass Center for Bioengineering, Hebrew University of Jerusalem, Jerusalem, Israel

    Triana Amen

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  1. Triana Amen
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Amen, T., Kaganovich, D. Dynamic droplets: the role of cytoplasmic inclusions in stress, function, and disease. Cell. Mol. Life Sci. 72, 401–415 (2015). https://doi.org/10.1007/s00018-014-1740-y

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