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Mitochondrial function - gatekeeper of intestinal epithelial cell homeostasis

Eva Rath1, Antonio Moschetta2,3, Dirk Haller4,5

  • 1Technische Universität München, Chair of Nutrition and Immunology, Freising, Germany.

Nature Reviews. Gastroenterology & Hepatology
|May 31, 2018
PubMed

Insights

Mitochondrial function is crucial for intestinal epithelial cell renewal and differentiation. Dysregulation of mitochondrial signaling and the mitochondrial unfolded protein response (MT-UPR) are linked to intestinal diseases like IBD and cancer.

Area of Science:

  • Gastroenterology
  • Cell Biology
  • Metabolic Signaling

Background:

  • The intestinal epithelium undergoes rapid self-renewal, with stem cells differentiating into various cell types.
  • Intestinal epithelial cells (IECs) exhibit distinct metabolic states during their differentiation journey.
  • Mitochondrial activity and signaling are integral to cellular processes within the gut.

Purpose of the Study:

  • To review the role of mitochondrial function and signaling in intestinal epithelial stemness and differentiation.
  • To explore the involvement of the mitochondrial unfolded protein response (MT-UPR) in IECs.
  • To highlight the implications of mitochondrial dysfunction in intestinal diseases.

Main Methods:

  • Literature review of studies on mitochondrial function in the intestinal epithelium.
  • Analysis of signaling pathways including MT-UPR and AMP kinase.
  • Examination of metabolic changes during IEC differentiation and in disease states.

Main Results:

  • Mitochondrial function influences cell fate decisions, metabolism, immunity, and apoptosis in IECs.
  • Mitochondrial signaling molecules (e.g., ATP, ROS) and pathways (e.g., MT-UPR) regulate cell cycle and stemness.
  • Altered mitochondrial function and MT-UPR activation are associated with inflammatory bowel disease (IBD) and cancer.

Conclusions:

  • Mitochondrial function acts as a critical checkpoint in maintaining intestinal homeostasis and regulating epithelial cell differentiation.
  • Mitochondrial signaling pathways are key regulators of stemness and lineage commitment in IECs.
  • Understanding mitochondrial roles offers insights into disease mechanisms and potential therapeutic targets for intestinal disorders.

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