TY - JOUR
T1 - Putting the brakes on autophagy
T2 - The role of heparan sulfate modified proteins in the balance of anabolic and catabolic pathways and intracellular quality control
AU - Schultheis, Nicholas
AU - Jiang, Mei
AU - Selleck, Scott B.
N1 - Funding Information:
This work described herein was supported in part by funds from NIH , the Cure Sanfilippo Foundation, and the Pennsylvania State University (SBS). We thank all present and past members of the laboratory that contributed to this work, Jeff Esko and Ryan Weiss for A375 cell reagents, and D. Zarnescu for transgenic hTDP-43 flies.
Publisher Copyright:
© 2021 The Author(s)
PY - 2021/6
Y1 - 2021/6
N2 - Autophagy is a fundamental cellular process discovered as a response to nutrient deprivation. It provides the cellular and molecular machinery for catabolism of cellular constituents, generating energy and providing building blocks for continued survival. However, autophagy does much more than provide an entry into catabolic pathways, it provides a mechanism for intracellular quality control, removing damaged organelles and misfolded proteins, processes critical for cellular health. Autophagy serves as a counterpoint to cell growth and anabolic events, activated when growth is not possible or is suppressed. Hence, there is an inherent antagonism between autophagy and growth. Heparan sulfate modified proteins are important co-receptors that generally promote growth factor activity and are therefore positioned within signaling networks that inhibit, or negatively regulate autophagy levels. This review summarizes evidence that heparan sulfate modified proteins provide an evolutionarily conserved inhibitory modulation of autophagy that can have profound effects on cell physiology and organismal responses to stress.
AB - Autophagy is a fundamental cellular process discovered as a response to nutrient deprivation. It provides the cellular and molecular machinery for catabolism of cellular constituents, generating energy and providing building blocks for continued survival. However, autophagy does much more than provide an entry into catabolic pathways, it provides a mechanism for intracellular quality control, removing damaged organelles and misfolded proteins, processes critical for cellular health. Autophagy serves as a counterpoint to cell growth and anabolic events, activated when growth is not possible or is suppressed. Hence, there is an inherent antagonism between autophagy and growth. Heparan sulfate modified proteins are important co-receptors that generally promote growth factor activity and are therefore positioned within signaling networks that inhibit, or negatively regulate autophagy levels. This review summarizes evidence that heparan sulfate modified proteins provide an evolutionarily conserved inhibitory modulation of autophagy that can have profound effects on cell physiology and organismal responses to stress.
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U2 - 10.1016/j.matbio.2021.01.006
DO - 10.1016/j.matbio.2021.01.006
M3 - Article
C2 - 33548399
AN - SCOPUS:85101326399
SN - 0945-053X
VL - 100-101
SP - 173
EP - 181
JO - Matrix Biology
JF - Matrix Biology
ER -