[摘要]:Mitochondria form reticular networks comprised of filamentous tubules and continuously move and change shape. Bcl-2 family proteins actively participate in the regulation of mitochondria fragmentation. Here, we show that human Noxa, which belongs to the BH3-only pro-apoptotic Bcl-2 family, causes mitochondrial fragmentation. We found that while the Bcl-2 homology 3 (BH3) domain of Noxa is not associated with mitochondrial fragmentation, the mitochondrial targeting domain (MTD) of Noxa is the region responsible for inducing fragmentation. Two leucine residues in MTD play a key role in the process. Furthermore, the lack of Noxa causes a significant reduction of Velcade-induced mitochondrial fragmentation. Together, these results provide novel insight into the role of Noxa in mitochondrial dynamics and cell death. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.