title: Cardiac ubiquitin ligases: Their role in cardiac metabolism, autophagy, cardioprotection and therapeutic potential.
abstract: Both the ubiquitin-proteasome system (UPS) and the lysosomal autophagy system have emerged as complementary key players responsible for the turnover of cellular proteins. The regulation of protein turnover is critical to cardiomyocytes as post-mitotic cells with very limited regenerative capacity. In this focused review, we describe the emerging interface between the UPS and autophagy, with E3's regulating autophagy at two critical points through multiple mechanisms. Moreover, we discuss recent insights in how both the UPS and autophagy can alter metabolism at various levels, to present new ways to think about therapeutically regulating autophagy in a focused manner to optimize disease-specific cardioprotection, without harming the overall homeostasis of protein quality control. This article is part of a Special Issue entitled: The role of post-translational protein modifications on heart and vascular metabolism edited by Jason R.B. Dyck & Jan F.C. Glatz.
authors.affiliation: McAllister Heart Institute, University of North Carolina, Chapel Hill, NC, USA; Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Traci L
authors.initials: TL
authors.lastname: Parry
authors.affiliation: McAllister Heart Institute, University of North Carolina, Chapel Hill, NC, USA; Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA; Department of Pharmacology, University of North Carolina, Chapel Hill, NC, USA. Electronic address: monte_willis@med.unc.edu.
authors.forename: Monte S
authors.initials: MS
authors.lastname: Willis
mesh_terms: D000818:Animals; D001343:Autophagy; D006331:Heart Diseases / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D006801:Humans; D008247:Lysosomes / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D011499:Protein Processing, Post-Translational; D000074702:Proteostasis; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D044767:Ubiquitin-Protein Ligases
keywords: Autophagy; Heart failure; Metabolism; Therapy; Ubiquitin ligases; Ubiquitin-proteasome system