Proteolethargy is a pathogenic mechanism in chronic disease
Name
moreno-shannong-phd-biology-2025-thesis .pdf
Description
Thesis PDF
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5.9 MB
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Adobe PDF
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60f8086fdd0c71aecc0c05665160d1bf
Author(s)
Moreno, Shannon
Advisor(s)
Young, Richard A.
Date Issued
May 2025
Publisher
Massachusetts Institute of Technology
Abstract
The pathogenic mechanisms of many diseases are well understood at the molecular level, but there are prevalent syndromes associated with pathogenic signaling, such as diabetes and chronic inflammation, where our understanding is more limited. Here, I present evidence that pathogenic signaling suppresses the mobility of a spectrum of proteins that play essential roles in cellular functions known to be dysregulated in these chronic diseases. The reduced protein mobility, which we call proteolethargy, was linked to cysteine residues in the affected proteins and signaling-related increases in excess reactive oxygen species. Diverse pathogenic stimuli, including hyperglycemia, dyslipidemia, and inflammation, produce similar reduced protein mobility phenotypes. I propose that proteolethargy is an overlooked cellular mechanism that may account for various pathogenic features of diverse chronic diseases.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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