title: An alternative import pathway of AIF to the mitochondria.
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.
authors: Graduate Institute of Microbiology and Public Health,Taichung,                     Taiwan, R.O.C.
authors: Shu-Fen
authors: SF
authors: Chiang
authors: Chih-Yang
authors: CY
authors: Huang
authors: Tze-Yi
authors: TY
authors: Lin
authors: Shiow-Her
authors: SH
authors: Chiou
authors: Kuan-Chih
authors: KC
authors: Chow
mesh_terms: D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D016195:G2 Phase; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport; D016196:S Phase; D014357:Trypsin / Q000378:metabolism
chemical_list: D051033:Apoptosis Inducing Factor; D014357:Trypsin