Myocardial glycogen dynamics: New perspectives on disease mechanisms. (April 2015)

• Record Type: Journal Article
• Authors: Chandramouli, Chanchal; Varma, Upasna; Stevens, Ellie M; Xiao, Rui‐Ping; Stapleton, David I; Mellor, Kimberley M; Delbridge, Lea MD
• Is Part Of: Clinical and experimental pharmacology and physiology. Volume 42:Number 4(2015:Apr.)
• Page Start: 415
• Page End: 425
• Publication Date: 2015-04
• Subjects: autophagy -- cardiac -- glucose -- glycogen storage diseases -- glycophagy -- heart -- metabolic stress; Clinical pharmacology -- Periodicals; Pharmacology, Experimental -- Periodicals; Physiology, Experimental -- Periodicals; Physiology, Pathological -- Periodicals; 615.1
• DOI: 10.1111/1440-1681.12370
• Languages: English
• ISSNs: 0305-1870

Abstract

Summary: Cardiac glycogen regulation involves a complex interplay between multiple signalling pathways, allosteric activation of enzymes, and sequestration for autophagic degradation. Signalling pathways appear to converge on glycogen regulatory enzymes via insulin (glycogen synthase kinase 3 β, protein phosphatase 1, allosteric action of glucose‐6‐phosphate), β –adrenergic (phosphorylase kinase protein phosphatase 1 inhibitor), and 5′ adenosine monophosphate‐activated protein kinase (allosteric action of glucose‐6‐phosphate, direct glycogen binding, insulin receptor). While cytosolic glycogen synthesis and breakdown are relatively well understood, recent findings relating to phagic glycogen degradation highlight a new area of investigation in the heart. It has been recently demonstrated that a specific glycophagy pathway is operational in the myocardium. Proteins involved in recruiting glycogen to the forming phagosome have been identified. Starch–binding domain‐containing protein 1 is involved in binding glycogen and mediating membrane anchorage via interaction with a homologue of the phagosomal protein light‐chain 3. Specifically, it has been shown that starch–binding domain‐containing protein 1 and light‐chain 3 have discrete phagosomal immunolocalization patterns in cardiomyocytes, indicating that autophagic trafficking of glycogen and protein cargo in cardiomyocytes can occur via distinct pathways. There is strong evidence from glycogen storage diseases that phagic/lysosomal glycogen breakdown is important for maintaining normal cardiac glycogen levels and does not simply constitute a redundant 'alternative' breakdown route for glycogen. Advancing understanding of glycogen handling in the heart is an important priority with relevance not only to genetic glycogen storage diseases but also to cardiac metabolic stress disorders such as diabetes and ischaemia.