Pre-clinical evidence for mitochondria as a therapeutic target for luteolin: A mechanistic view

Pre-clinical evidence indicates that mitochondria may be a therapeutic target for luteolin (3′,4’,5,7-tetrahydroxyflavone; LUT) in different conditions. LUT modulates mitochondrial physiology in in vitro , ex vivo , and in vivo experimental models. This flavone exerted mitochondria-related antioxidant and anti-apoptotic effects, stimulated mitochondrial fusion and fission, induced mitophagy, and promoted mitochondrial biogenesis in human and animal cells and tissues. Moreover, LUT modulated the activity of components of the oxidative phosphorylation (OXPHOS) system, improving the ability of mitochondria to produce adenosine triphosphate (ATP) in certain circumstances. The mechanism of action by which LUT promoted mitochondrial benefits and protection are not completely clear yet. Nonetheless, LUT is a potential candidate to be utilized in mitochondrial therapy in the future. In this work, it is explored the mechanisms of action by which LUT modulates mitochondrial physiology in different pre-clinical experimental models. Major effects of luteolin (LUT) on mitochondrial physiology. LUT promote mitochondrial protection by a myriad of mechanisms. This flavone exerts redox-related actions on the mitochondria by stimulating the expression and by increasing the activity of antioxidant enzymes and by reducing the production of reactive species by the organelles. LUT also attenuates mitochondria-dependent triggering of cell death. Mitochondrial dynamics ( i.e. , fusion and fission) can be modulated by LUT in response to several stimuli. Moreover, mitophagy is promoted by LUT as part of the adaptation to stress, among other scenarios. Evidence point to LUT as an inducer of mitochondrial biogenesis, rendering benefits to human and animal cells. Figure created by using an image obtained from Servier Medical Art, licensed under a Creative Commons Attribution 4.0 Unported License ( https://creativecommons.org/licenses/by/4.0/ ). • LUT exerts cytoprotection in different cell types. • LUT modulates mitochondrial function and dynamics. • LUT stimulates mitochondrial biogenesis. • Mitophagy is induced by LUT as part of the adaptation to stress. • Mitochondria may be therapeutic targets for LUT.