Mitochondrial remodeling and energy metabolism adaptations in colonic crypts during spontaneous epithelial repair after colitis induction in mice

• Published in: Free radical biology & medicine Vol. 205; pp. 224 - 233
• Main Authors: Lan, Annaïg, Guerbette, Thomas, Andriamihaja, Mireille, Magnin, Benjamin, Bordet, Martin, Ferron, Pierre-Jean, Burel, Agnès, Viel, Roselyne, Fromenty, Bernard, Corlu, Anne, Blachier, François, Bouguen, Guillaume
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.08.2023; Elsevier
• Subjects: Adenosine Triphosphate - metabolism; Animals; Colitis - chemically induced; Colitis - genetics; Colon - metabolism; Colon epithelium; Dextran Sulfate; Disease Models, Animal; DSS-Induced colitis; Energy Metabolism; Inflammation - metabolism; Intestinal Mucosa - metabolism; Life Sciences; Mice; Mice, Inbred C57BL; Mitochondria - metabolism; Mitochondrial respiration and dynamics; Oxidative stress response; Spontaneous epithelial repair; Spontaneous epithelial repair; DSS-Induced colitis; Mitochondrial respiration and dynamics; Oxidative stress response; Colon epithelium
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2023.06.007

Mucosal healing has emerged as a therapeutic goal to achieve lasting clinical remission in ulcerative colitis. Intestinal repair in response to inflammation presumably requires higher energy supplies for the restoration of intestinal barrier and physiological functions. However, epithelial energy metabolism during intestinal mucosal healing has been little studied, whereas inflammation-induced alterations have been reported in the main energy production site, the mitochondria. The aim of the present work was to assess the involvement of mitochondrial activity and the events influencing their function during spontaneous epithelial repair after colitis induction in mouse colonic crypts. The results obtained show adaptations of colonocyte metabolism during colitis to ensure maximal ATP production for supporting energetic demand by both oxidative phosphorylation and glycolysis in a context of decreased mitochondrial biogenesis and through mitochondrial function restoration during colon epithelial repair. In parallel, colitis-induced mitochondrial ROS production in colonic epithelial cells was rapidly associated with transient expression of GSH-related enzymes. Mitochondrial respiration in colonic crypts was markedly increased during both inflammatory and recovery phases despite decreased expression of several mitochondrial respiratory chain complex subunits after colitis induction. Rapid induction of mitochondrial fusion was associated with mitochondrial function restoration. Finally, in contrast with the kinetics expression of genes involved in mitochondrial oxidative metabolism and in glycolysis, the expression of glutaminase was markedly reduced in the colonic crypts both during colitis and repair phases. Overall, our data suggest that the epithelial repair after colitis induction is characterized by a rapid and transient increased capacity for mitochondrial ATP production in a context of apparent restoration of mitochondrial biogenesis and metabolic reorientation of energy production. The potential implication of energy production adaptations within colonic crypts to sustain mucosal healing in a context of altered fuel supply is discussed. [Display omitted] •This study shows metabolic adaptations of colonocytes to reach maximal energy production potential in order to sustain energetic demand during colitis and colon epithelial repair.•Although mitochondria morphology and expression of genes related to mitochondrial function are severely impacted by inflammation, capacity of oxidative phosphorylation in colonic crypts remains active at all stages of colitis and repair.•Strong antioxidant response is induced in colon crypts following colitis induction, in association with a long-lasting generation reduction of reactive oxygen species in mitochondria despite a high respiratory chain activity.