title: Mitochondrial defects lie at the basis of neutropenia in Barth syndrome.
abstract: OBJECTIVE
  Barth syndrome (BTHS) is a mitochondrial disorder characterized by neutropenia, among other defects. As yet, the correlation between the mitochondrial defect in BTHS and the neutropenia observed in these patients is unclear. In this review, we hope to shed some light upon the correlation between the metabolic properties of neutrophil mitochondria and their susceptibility to the defects observed in BTHS.
  
  
  RESULTS
  BTHS neutrophils avidly expose phosphatidyl serine, a phospholipid that is normally restrained to the inner leaflet of the plasma membrane. Although phosphatidyl serine exposure is usually considered to be a marker for apoptosis, BTHS neutrophils have no other apoptotic features and function normally. It has recently become clear that the respiratory chain in all BTHS tissues lacks super-complex organization, leading to inefficient electron transport. In neutrophils, the super-complex organization of the respiratory chain is disturbed by default, even in healthy individuals. Further disturbance in BTHS patients may lie at the basis of their neutropenia.
  
  
  CONCLUSIONS
  It seems unlikely that neutropenia in BTHS is caused by apoptosis of the myeloid precursor cells or end-stage neutrophils. Instead, mitochondria-derived reactive oxygen species may act as signaling intermediates that trigger phosphatidyl serine exposure. This, in turn, appears to lead to increased clearance of neutrophils by tissue macrophages.
authors.affiliation: Sanquin Research and Landsteiner Laboratory, Department of Blood Cell Research, University of Amsterdam, the Netherlands.
authors.forename: Bram J
authors.initials: BJ
authors.lastname: van Raam
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
mesh_terms: D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D028361:Mitochondrial Diseases / Q000378:metabolism / Q000473:pathology*; D009503:Neutropenia / Q000209:etiology*; D009504:Neutrophils / Q000473:pathology / Q000648:ultrastructure; D010718:Phosphatidylserines / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013577:Syndrome
chemical_list: D010718:Phosphatidylserines; D017382:Reactive Oxygen Species