Exercise-induced lactylation A novel mechanism regulating mitochondria-lipid droplet interaction and energy homeostasis
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The exercise-induced rise in lactate is traditionally considered a by-product of metabolism, which triggers a metabolism-regulating post-translational modification, lactylation. The dynamic properties of lactylation during physical exercise and how this biological process occurs in mitochondria-lipid droplet interactions are summarized in this review. Based on emerging evidence primarily from non-exercise models, lactylation has been proposed as a potential carrier of metabolic memory. It may facilitate phase separation to enhance communication efficiency, mediate metabolic crosstalk within the muscle-adipose axis, and add a new dimension of regulation in exercise metabolism. However, these functions remain hypothetical in the context of exercise and require validation in physiologically relevant models. These mechanisms include altered perilipin 5 (PLIN5) that facilitates contact between organelles to use fatty acids and lactylation deficiency that has adverse effects on lipid homeostasis. Lactylation is a competing mechanism with acetylation in the control of metabolic reactions. Despite some significant progress, major gaps remain in our understanding of the precise regulatory processes of lactylation, its relationships with other signalling pathways, and whether it can be used therapeutically. This research summarizes the modern results, carefully analyses the existing issues, and proposes the future research directions, which may be used as a source of extensive study in this field.
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