Metabolic reprogramming and membrane glycan remodeling as potential drivers of zebrafish heart regeneration

Author:

Spelat RenzaORCID,Ferro FedericoORCID,Contessotto Paolo,Aljaabary AmalORCID,Martin-Saldaña SergioORCID,Jin ChunshengORCID,Karlsson Niclas G.ORCID,Grealy Maura,Hilscher Markus M.ORCID,Magni Fulvio,Chinello Clizia,Kilcoyne MichelleORCID,Pandit AbhayORCID

Abstract

AbstractThe ability of the zebrafish heart to regenerate following injury makes it a valuable model to deduce why this capability in mammals is limited to early neonatal stages. Although metabolic reprogramming and glycosylation remodeling have emerged as key aspects in many biological processes, how they may trigger a cardiac regenerative response in zebrafish is still a crucial question. Here, by using an up-to-date panel of transcriptomic, proteomic and glycomic approaches, we identify a metabolic switch from mitochondrial oxidative phosphorylation to glycolysis associated with membrane glycosylation remodeling during heart regeneration. Importantly, we establish the N- and O-linked glycan structural repertoire of the regenerating zebrafish heart, and link alterations in both sialylation and high mannose structures across the phases of regeneration. Our results show that metabolic reprogramming and glycan structural remodeling are potential drivers of tissue regeneration after cardiac injury, providing the biological rationale to develop novel therapeutics to elicit heart regeneration in mammals.

Funder

Science Foundation Ireland

Publisher

Springer Science and Business Media LLC

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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