title: The radical-binding lipocalin A1M binds to a Complex I subunit and protects mitochondrial structure and function.
abstract: OBJECTIVE
  During cell death, energy-consuming cell degradation and recycling programs are performed. Maintenance of energy delivery during cell death is therefore crucial, but the mechanisms to keep the mitochondrial functions intact during these processes are poorly understood. We have investigated the hypothesis that the heme- and radical-binding ubiquitous protein α1-microglobulin (A1M) is involved in protection of the mitochondria against oxidative insult during cell death.
  
  
  RESULTS
  Using blood cells, keratinocytes, and liver cells, we show that A1M binds with high affinity to apoptosis-induced cells and is localized to mitochondria. The mitochondrial Complex I subunit NDUFAB1 was identified as a major molecular target of the A1M binding. Furthermore, A1M was shown to inhibit the swelling of mitochondria, and to reverse the severely abrogated ATP-production of mitochondria when exposed to heme and reactive oxygen species (ROS).
  
  
  METHODS
  Import of the radical- and heme-binding protein A1M from the extracellular compartment confers protection of the mitochondrial structure and function during cellular insult.
  
  
  CONCLUSIONS
  A1M binds to a subunit of Complex I and has a role in assisting the mitochondria to maintain its energy delivery during cell death. A1M may also, at the same time, counteract and eliminate the ROS generated by the mitochondrial respiration to prevent oxidative damage to surrounding healthy tissue.
authors.affiliation: Division of Infection Medicine, Lund University, Lund, Sweden. magnus.gram@med.lu.se
authors.forename: Magnus G
authors.initials: MG
authors.lastname: Olsson
authors.forename: Lena W
authors.initials: LW
authors.lastname: Rosenlöf
authors.forename: Heike
authors.initials: H
authors.lastname: Kotarsky
authors.forename: Tor
authors.initials: T
authors.lastname: Olofsson
authors.forename: Tomas
authors.initials: T
authors.lastname: Leanderson
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.forename: Vineta
authors.initials: V
authors.lastname: Fellman
authors.forename: Bo
authors.initials: B
authors.lastname: Åkerström
mesh_terms: D000510:Alpha-Globulins / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D042967:Electron Transport Complex I / Q000378:metabolism*; D006801:Humans; D054834:Lipocalins / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding
chemical_list: D000510:Alpha-Globulins; D054834:Lipocalins; C016001:alpha-1-microglobulin; D042967:Electron Transport Complex I