Cellular responses to proteostasis perturbations reveal non-optimal feedback in chaperone networks.

Cellular responses to proteostasis perturbations reveal non-optimal feedback in chaperone networks.
Cell Mol Life Sci. 2019 Jan 25;:
Authors: Ghosh A, Gangadharan A, Verma M, Das S, Matai L, Dash DP, Dash D, Mapa K, Chakraborty K
Abstract
The proteostasis network (PN) comprises a plethora of proteins that are dedicated to aid in protein folding and maintenance; some with overlapping functions. Despite this, there are multiple pathophysiological states associated with depletion of chaperones. This is counter-intuitive, assuming cells have the ability to re-program transcriptional outputs in accordance with its proteostasic limitations. Here, we have used S. cerevisiae to understand how cells respond to different types of proteostasis impairments. We monitored the proteostasis status and transcriptome of single deletions of fourteen different Protein Quality Control (PQC) genes. In most cases, cellular response did not activate proteostasis components or pathways that could either complement the function of the missing PQC gene or restore proteostasis. Over-expression of alternate machineries could restore part of the proteostasis defect in two representative PQC gene deletion strains. We posit that S. cerevisiae inherently lacks the ability to sense and respond optimally to defects in proteostasis caused due to deletion of specific PQC components.
PMID: 30683983 [PubMed - as supplied by publisher]

Source: Cellular and Molecular Life Sciences : CMLS - January 25, 2019 Category: Cytology Authors: Ghosh A, Gangadharan A, Verma M, Das S, Matai L, Dash DP, Dash D, Mapa K, Chakraborty K Tags: Cell Mol Life Sci Source Type: research