An alternative import pathway of AIF to the mitochondria

  • Authors:
    • Shu-Fen Chiang
    • Chih-Yang Huang
    • Tze-Yi Lin
    • Shiow-Her Chiou
    • Kuan-Chih Chow
  • View Affiliations

  • Published online on: November 29, 2011     https://doi.org/10.3892/ijmm.2011.849
  • Pages: 365-372
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Abstract

In eukaryotic cells, transport of the newly synthesized proteins and phospholipids to the appropriate subcellular target compartments is essential for maintaining organelle morphology and cell survival. In animal cells, mitochondria are major organelles containing DNA genome that encodes only for a small fraction of their proteins, which are required for the organelle function. Most mitochondrial proteins are encoded by the nuclear genes and imported to the mitochondria following protein synthesis. Apoptosis-inducing factor (AIF), an essential FAD-dependent NADH oxidase for the oxidative phosphorylation, is located in the intermembranous space and contains mitochondrial localization signals. However, the import mechanism of AIF to the mitochondria is not yet studied. Using sucrose gradient ultracentrifugation and immunoblotting, AIF was detected in fractions of the endoplasmic reticulum, mitochondria-associated membranes (MAM) and mitochondria, and AIF from these fractions was resistant to trypsin in the absence of digitonin, suggesting that AIF could be protected by phospholipids. Knockdown of dynamin-related protein 1 (DRP1kd) expression reduced AIF levels in the mitochondria, but increased AIF concentrations in the MAM. Knockdown of mitofusin-2 (Mfn-2kd) or ATPase family AAA domain containing 3A (ATAD3Akd) expression, however, reduced AIF levels in the mitochondria and increased the number of transport vesicles that contained AIF in the cytosol, indicating that ATAD3A and Mfn-2 were respectively essential for the import and fusion of transport vesicles into the mitochondria. Here we show that AIF is imported from the endoplasmic reticulum to the mitochondria via mitochondria-associated membranes and transport vesicles.

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March 2012
Volume 29 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Chiang S, Huang C, Lin T, Chiou S and Chow K: An alternative import pathway of AIF to the mitochondria. Int J Mol Med 29: 365-372, 2012
APA
Chiang, S., Huang, C., Lin, T., Chiou, S., & Chow, K. (2012). An alternative import pathway of AIF to the mitochondria. International Journal of Molecular Medicine, 29, 365-372. https://doi.org/10.3892/ijmm.2011.849
MLA
Chiang, S., Huang, C., Lin, T., Chiou, S., Chow, K."An alternative import pathway of AIF to the mitochondria". International Journal of Molecular Medicine 29.3 (2012): 365-372.
Chicago
Chiang, S., Huang, C., Lin, T., Chiou, S., Chow, K."An alternative import pathway of AIF to the mitochondria". International Journal of Molecular Medicine 29, no. 3 (2012): 365-372. https://doi.org/10.3892/ijmm.2011.849