Effects of the BH3-only protein human Noxa on mitochondrial dynamics.
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.
Woo
Ha-Na
HN
Institute for Innovative Cancer Research, Asan Medical Center, Pungnap2-Dong, Songpa-Gu, Seoul 138-736, Republic of Korea.
Seo
Young-Woo
YW
Moon
Ae Ran
AR
Jeong
Seon-Yong
SY
Jeong
Seong-Yun
SY
Choi
Eun Kyung
EK
Kim
Tae-Hyoung
TH
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
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