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.

Abbreviations: BH3 domain, Bcl-2 homology domain 3, MTD, mitochondrial targeting domain

Keywords: BH3-only protein, Noxa, Mitochondrial targeting domain, Mitochondrial fragmentation