Apoptosis-inducing factor

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Function

Apoptosis-inducing factor (AIF) is an intermembrane flavoprotein which induces caspase-independent peripheral chromatin condensation and large-scale DNA fragmentation and thus causes cell death[1]. AIF contains the cofactor FAD.

Relevance

AIF deficiency is a risk factor for the development of diabetic kidney disease[2].

Structural highlights

The AIF binding site contains the cofactor FAD and 2 molecules of the reducing factor NADH[3]. Water molecules shown as red spheres.

  • 1st NADH binding site.
  • 2nd NADH binding site.
  • FAD/1st molecule NADF tunnel.
  • 2nd NADH binding site in surface representation.


Human apoptosis-inducing factor complex with FAD, NAD and sulfate (PDB code 4bur)

Drag the structure with the mouse to rotate

3D structures of apoptosis-inducing factor see CED-8 in Cell death protein

References

  1. Cande C, Cohen I, Daugas E, Ravagnan L, Larochette N, Zamzami N, Kroemer G. Apoptosis-inducing factor (AIF): a novel caspase-independent death effector released from mitochondria. Biochimie. 2002 Feb-Mar;84(2-3):215-22. PMID:12022952
  2. Coughlan MT, Higgins GC, Nguyen TV, Penfold SA, Thallas-Bonke V, Tan SM, Ramm G, Van Bergen NJ, Henstridge DC, Sourris KC, Harcourt BE, Trounce IA, Robb PM, Laskowski A, McGee SL, Genders AJ, Walder K, Drew BG, Gregorevic P, Qian H, Thomas MC, Jerums G, Macisaac RJ, Skene A, Power DA, Ekinci EI, Wijeyeratne XW, Gallo LA, Herman-Edelstein M, Ryan MT, Cooper ME, Thorburn DR, Forbes JM. Deficiency in Apoptosis-Inducing Factor Recapitulates Chronic Kidney Disease via Aberrant Mitochondrial Homeostasis. Diabetes. 2016 Apr;65(4):1085-98. doi: 10.2337/db15-0864. Epub 2016 Jan 28. PMID:26822084 doi:http://dx.doi.org/10.2337/db15-0864
  3. Ferreira P, Villanueva R, Martinez-Julvez M, Herguedas B, Marcuello C, Fernandez-Silva P, Cabon L, Hermoso JA, Lostao A, Susin SA, Medina M. Structural insights into the coenzyme mediated monomer-dimer transition of the pro-apoptotic apoptosis inducing factor. Biochemistry. 2014 Jul 1;53(25):4204-15. doi: 10.1021/bi500343r. Epub 2014 Jun, 20. PMID:24914854 doi:http://dx.doi.org/10.1021/bi500343r

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