Phosphorylation Modifications Regulating Cardiac Protein Quality Control Mechanisms

Autor: Sumita Mishra, Brittany L. Dunkerly-Eyring, Gizem Keceli, Mark J. Ranek
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Frontiers in Physiology, Vol 11 (2020)
Druh dokumentu: article
ISSN: 1664-042X
DOI: 10.3389/fphys.2020.593585
Popis: Many forms of cardiac disease, including heart failure, present with inadequate protein quality control (PQC). Pathological conditions often involve impaired removal of terminally misfolded proteins. This results in the formation of large protein aggregates, which further reduce cellular viability and cardiac function. Cardiomyocytes have an intricately collaborative PQC system to minimize cellular proteotoxicity. Increased expression of chaperones or enhanced clearance of misfolded proteins either by the proteasome or lysosome has been demonstrated to attenuate disease pathogenesis, whereas reduced PQC exacerbates pathogenesis. Recent studies have revealed that phosphorylation of key proteins has a potent regulatory role, both promoting and hindering the PQC machinery. This review highlights the recent advances in phosphorylations regulating PQC, the impact in cardiac pathology, and the therapeutic opportunities presented by harnessing these modifications.
Databáze: Directory of Open Access Journals