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標題: An alternative import pathway of AIF to the mitochondria
作者: Chiang, S.F.
Huang, C.Y.
Lin, T.Y.
Chiou, S.H.
Chow, K.C.
關鍵字: ATPase family AAA domain containing 3A;dynamin-related protein 1;endoplasmic reticulum;mitofusin-2;mitochondria;mitochondria-associated membrane;programmed cell death protein 8;transport vesicles;apoptosis-inducing factor;dynamin-related protein-1;cytochrome-c-oxidase;endoplasmic-reticulum;mammalian-cells;membrane;peroxisomes;expression;transport;subunits
Project: International Journal of Molecular Medicine
期刊/報告no:: International Journal of Molecular Medicine, Volume 29, Issue 3, Page(s) 365-372.
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 (DRPIkd) expression reduced AIF levels in the mitochondria, but increased AIF concentrations in the MAM. Knockdown of mitofusin-2 (Mfn-2(kd)) or ATPase family AAA domain containing 3A (ATAD3A(kd)) 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.
ISSN: 1107-3756
DOI: 10.3892/ijmm.2011.849
Appears in Collections:期刊論文

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