Cellular Protein Quality Control in Diabetic Cardiomyopathy: From Bench to Bedside

Frontiers in Cardiovascular Medicine
Namrita KaurWei Liu

Abstract

Heart failure is a serious comorbidity and the most common cause of mortality in diabetes patients. Diabetic cardiomyopathy (DCM) features impaired cellular structure and function, culminating in heart failure; however, there is a dearth of specific clinical therapy for treating DCM. Protein homeostasis is pivotal for the maintenance of cellular viability under physiological and pathological conditions, particularly in the irreplaceable cardiomyocytes; therefore, it is tightly regulated by a protein quality control (PQC) system. Three evolutionarily conserved molecular processes, the unfolded protein response (UPR), the ubiquitin-proteasome system (UPS), and autophagy, enhance protein turnover and preserve protein homeostasis by suppressing protein translation, degrading misfolded or unfolded proteins in cytosol or organelles, disposing of damaged and toxic proteins, recycling essential amino acids, and eliminating insoluble protein aggregates. In response to increased cellular protein demand under pathological insults, including the diabetic condition, a coordinated PQC system retains cardiac protein homeostasis and heart performance, on the contrary, inappropriate PQC function exaggerates cardiac proteotoxicity with subsequen...Continue Reading

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Citations

Feb 3, 2021·European Journal of Clinical Investigation·Thamonwan DiteepengMarco Luciani
Apr 11, 2021·Ageing Research Reviews·Saikat DewanjeeRamesh Kandimalla

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Methods Mentioned

BETA
protein folding
fluorescence imaging
nucleotide exchange
glycosylation
lipidation
GTPases
ubiquitination

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