title: Effects of the BH3-only protein human Noxa on mitochondrial dynamics.
abstract: 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.
authors.affiliation: Institute for Innovative Cancer Research, Asan Medical Center, Pungnap2-Dong, Songpa-Gu, Seoul 138-736, Republic of Korea.
authors.forename: Ha-Na
authors.initials: HN
authors.lastname: Woo
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Seo
authors.forename: Ae Ran
authors.initials: AR
authors.lastname: Moon
authors.forename: Seon-Yong
authors.initials: SY
authors.lastname: Jeong
authors.forename: Seong-Yun
authors.initials: SY
authors.lastname: Jeong
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Choi
authors.forename: Tae-Hyoung
authors.initials: TH
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001897:Boronic Acids / Q000378:metabolism; D000069286:Bortezomib; D016923:Cell Death / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D007930:Leucine / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D011719:Pyrazines / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D001897:Boronic Acids; C498702:PMAIP1 protein, human; D011480:Protease Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D011719:Pyrazines; D051028:bcl-2-Associated X Protein; D000069286:Bortezomib; D007930:Leucine