The radical-binding lipocalin A1M binds to a Complex I subunit and protects mitochondrial structure and function.
Författare
Summary, in English
Aims: 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 A1M (α<sub>1</sub>-microglobulin) 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 ROS. Innovation: Import of the radical- and heme-binding protein A1M from the extracellular compartment confers protection of mitochondrial structure and function during cellular insult. Conclusion: 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.
Avdelning/ar
Publiceringsår
2013
Språk
Engelska
Sidor
2017-2028
Publikation/Tidskrift/Serie
Antioxidants & Redox Signaling
Volym
18
Issue
16
Fulltext
- Available as PDF - 899 kB
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Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Mary Ann Liebert, Inc.
Ämne
- Cell and Molecular Biology
Status
Published
Forskningsgrupp
- Immunology
- Redox Medicine
ISBN/ISSN/Övrigt
- ISSN: 1557-7716