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AbstractPerturbations in metabolic processes are associated with diseases such as obesity, type 2 diabetes mellitus, certain infections and some cancers. A resurgence of interest in creatine biology is developing, with new insights into a diverse set of regulatory functions for creatine. This resurgence is primarily driven by technological advances in genetic engineering and metabolism as well as by the realization that this metabolite has key roles in cells beyond the muscle and brain. Herein, we highlight the latest advances in creatine biology in tissues and cell types that have historically received little attention in the field. In adipose tissue, creatine controls thermogenic respiration and loss of this metabolite impairs whole-body energy expenditure, leading to obesity. We also cover the various roles that creatine metabolism has in cancer cell survival and the function of the immune system. Renewed interest in this area has begun to showcase the therapeutic potential that lies in understanding how changes in creatine metabolism lead to metabolic disease.
Key points
Mitochondria in brown adipose tissue are capable of normal oxidative phosphorylation, with P:O ratios similar to those of other tissues.
Atypical actions of creatine involve phosphocreatine transport into colorectal cancer cells, super-stoichiometric ADP liberation to trigger respiration in thermogenic adipocytes and chromatin remodelling to modulate macrophage polarity.
Cyclocreatine and creatine can both inhibit tumour progression, suggesting that the pro-cancer role of creatine is independent of its function in energy buffering.
The mitochondrial network transduces energy over long distances, thus minimizing the requirement for metabolite diffusion, whereas cells with a disrupted mitochondrial network might buffer energy via the creatine kinase–phosphocreatine circuit
Edited by Nigeria Custom Officer, 08 June 2020 - 08:37 AM.
