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Bacterial muropeptides promote OXPHOS and suppress mitochondrial stress in mammals

Dong Tian1, Mingxue Cui1, Min Han1

  • 1Department of MCDB, University of Colorado at Boulder, Boulder, CO 80309, USA.

Cell Reports
|April 7, 2024
PubMed

Insights

Bacterial peptidoglycan muropeptides enhance mitochondrial function, improving cellular energy production and mitigating disease phenotypes. This discovery offers a potential therapeutic strategy for mitochondrial disorders.

Area of Science:

  • Microbiology
  • Cell Biology
  • Metabolic Diseases

Background:

  • Mitochondrial dysfunction is implicated in numerous human diseases.
  • The role of gut microbial metabolites in animal mitochondrial function is not well understood.

Purpose of the Study:

  • To investigate the impact of bacterial peptidoglycan muropeptides on mammalian mitochondrial function.
  • To elucidate the mechanisms by which muropeptides influence mitochondrial homeostasis.

Main Methods:

  • Treatment of human intestinal epithelial cells and patient-derived fibroblasts with muropeptides.
  • In vivo studies in mice to assess muropeptide effects on intestinal homeostasis.
  • In vitro biochemical assays to determine muropeptide interaction with ATP synthase.

Main Results:

  • Muropeptides increased oxidative respiration and ATP production in human intestinal epithelial cells.
  • Muropeptide treatment restored mitochondrial structure and function in patient-derived cells.
  • Muropeptides were found to accumulate in mitochondria, promoting intestinal homeostasis and nutrient absorption in mice.
  • Muropeptides directly bind to and activate ATP synthase in vitro.

Conclusions:

  • Bacterial peptidoglycan muropeptides significantly promote mitochondrial function across various mammalian models.
  • Muropeptides act as agonists of ATP synthase, contributing to mitochondrial homeostasis.
  • This research presents muropeptides as a potential therapeutic avenue for human mitochondrial diseases.
Keywords:
ATP synthaseCP: Cell biologyCP: MetabolismLeigh syndromePGNROSantibiotic-induced microbiome depletionelectron transfer chainenergy metabolismintestinal epithelial cellsintestinal homeostasismitochondrial diseasesoxidative phosphorylationoxidative stresspeptidoglycan

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