Autophagy and mitochondrial remodelling in mouse mesenchymal stromal cells challenged with Staphylococcus epidermidis

J Cell Mol Med. 2015 May;19(5):1133-50. doi: 10.1111/jcmm.12518. Epub 2015 Feb 26.

Abstract

The bone marrow stroma constitutes the marrow-blood barrier, which sustains immunochemical homoeostasis and protection of the haematopoietic tissue in sequelae of systemic bacterial infections. Under these conditions, the bone marrow stromal cells affected by circulating bacterial pathogens shall elicit the adaptive stress-response mechanisms to maintain integrity of the barrier. The objective of this communication was to demonstrate (i) that in vitro challenge of mesenchymal stromal cells, i.e. colony-forming unit fibroblasts (CFU-F), with Staphylococcus epidermidis can activate the autophagy pathway to execute antibacterial defence response, and (ii) that homoeostatic shift because of the bacteria-induced stress includes the mitochondrial remodelling and sequestration of compromised organelles via mitophagy. Implication of Drp1 and PINK1-PARK2-dependent mechanisms in the mitophagy turnover of the aberrant mitochondria in mesenchymal stromal cells is investigated and discussed.

Keywords: Staphylococcus epidermidis; autophagy; mesenchymal stromal cells; mitochondria; stress response.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autophagy / genetics
  • Autophagy / physiology*
  • Cells, Cultured
  • Dynamins / genetics
  • Dynamins / metabolism
  • Gene Expression
  • Host-Pathogen Interactions
  • Immunoblotting
  • Lysosomes / metabolism
  • Lysosomes / ultrastructure
  • Mesenchymal Stem Cells / metabolism*
  • Mesenchymal Stem Cells / microbiology
  • Mesenchymal Stem Cells / ultrastructure
  • Microscopy, Confocal
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Mitophagy / genetics
  • Mitophagy / physiology
  • Phagosomes / metabolism
  • Phagosomes / ultrastructure
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics
  • Staphylococcus epidermidis / growth & development*
  • Staphylococcus epidermidis / physiology
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Ubiquitin-Protein Ligases
  • parkin protein
  • Protein Kinases
  • PTEN-induced putative kinase
  • Dnm1l protein, mouse
  • Dynamins