Mitochondria form intricate networks through fission and fusion events. Here, we identify mitochondrial dynamics proteins of 49 and 51 kDa (MiD49 and MiD51, respectively) anchored in the mitochondrial outer membrane. MiD49/51 form foci and rings around mitochondria similar to the fission mediator dynaminrelated protein 1 (Drp1). MiD49/51 directly recruit Drp1 to the mitochondrial surface, whereas their knockdown reduces Drp1 association, leading to unopposed fusion. Overexpression of MiD49/51 seems to sequester Drp1 from functioning at mitochondria and cause fused tubules to associate with actin. Thus, MiD49/51 are new mediators of mitochondrial division affecting Drp1 action at mitochondria.

The cytokine TWEAK and its cognate receptor Fn14 are members of the TNF/TNFR superfamily and are upregulated in tumors. We found that Fn14, when expressed in tumors, causes cachexia and that antibodies against Fn14 dramatically extended lifespan by inhibiting tumor-induced weight loss although having only moderate inhibitory effects on tumor growth. Anti-Fn14 antibodies prevented tumor-induced inflammation and loss of fat and muscle mass. Fn14 signaling in the tumor, rather than host, is responsible for inducing this cachexia because tumors in Fn14- and TWEAK-deficient hosts developed cachexia that was comparable to that of wild-type mice. These results extend the role of Fn14 in wound repair and muscle development to involvement in the etiology of cachexia and indicate that Fn14 antibodies may be a promising approach to treat cachexia, thereby extending lifespan and improving quality of life for cancer patients.

During acute measles virus (MV) infection

Measles virus (MV) nucleoprotein (N) is a cytosolic protein that is released into the extracellular compartment after apoptosis and/or secondary necrosis of MV-infected cells in vitro. Thus, MV-N becomes accessible to inhibitory cell-surface receptors: FcγRIIB and an uncharacterized nucleoprotein receptor (NR). MV-N is composed of two domains: NCORE (aa 1–400) and NTAIL (aa 401–525). To assess the contribution of MV-N domains and of these two receptors in suppression of cell proliferation, a human melanoma HT144 cell line expressing (HT144IIB1) or lacking FcγRIIB1 was used as a model. Specific and exclusive NCORE–FcγRIIB1 and NTAIL–NR interactions were shown. Moreover, NTAIL binding to human NR predominantly led to suppression of cell proliferation by arresting cells in the G0/G1 phases of the cell cycle, rather than to apoptosis. NCORE binding to HT144IIB1 cells primarily triggered caspase-3 activation, in contrast to HT144IIB1/IC− cells lacking the FcγRIIB1 intra-cytoplasmic tail, thus demonstrating the specific inhibitory effect of the NCORE–FcγRIIB1 interaction. MV-N- and NCORE-mediated apoptosis through FcγRIIB1 was inhibited by the pan-caspase inhibitor zVAD-FMK, indicating that apoptosis was dependent on caspase activation. By using NTAIL deletion proteins, it was also shown that the region of NTAIL responsible for binding to human NR and for cell growth arrest maps to one of the three conserved boxes (Box1, aa 401–420) found in N of Morbilliviruses. This work unveils novel mechanisms by which distinct domains of MV-N may display different immunosuppressive activities, thus contributing to our comprehension of the immunosuppressive state associated with MV infection. Finally, MV-N domains may be good tools to target tumour cell proliferation and/or apoptosis.