Uniparental mitochondrial DNA inheritance is not affected in Ustilago maydis Δatg11 mutants blocked in mitophagy

Background: Maternal or uniparental inheritance (UPI) of mitochondria is generally observed in sexual eukaryotes, however, the underlying mechanisms are diverse and largely unknown. Recently, based on the use of mutants blocked in autophagy, it has been demonstrated that autophagy is required for strict maternal inheritance in the nematode Caenorhabditis elegans. Uniparental mitochondrial DNA (mtDNA) inheritance has been well documented for numerous fungal species, and in particular, has been shown to be genetically governed by the mating-type loci in the isogamous species Cryptococcus neoformans, Phycomyces blakesleeanus and Ustilago maydis. Previously, we have shown that the a2 mating-type locus gene lga2 is decisive for UPI during sexual development of U. maydis. In axenic culture, conditional overexpression of lga2 triggers efficient loss of mtDNA as well as mitophagy. To assess a functional relationship, we have investigated UPI in U. maydis Δatg11 mutants, which are blocked in mitophagy. Results: This study has revealed that Äatg11 mutants are not affected in pathogenic development and this has allowed us to analyse UPI under comparable developmental conditions between mating-compatible wild-type and mutant strain combinations. Explicitly, we have examined two independent strain combinations that gave rise to different efficiencies of UPI. We demonstrate that in both cases UPI is atg11-independent, providing evidence that mitophagy is not critical for UPI in U. maydis, even under conditions of strict UPI. Conclusions: Until now, analysis of a role of mitophagy in UPI has not been reported for microbial species. Our study suggests that selective autophagy does not contribute to UPI in U. maydis, but is rather a consequence of selective mtDNA elimination in response to mitochondrial damage. © 2015 Wagner-Vogel et al.; licensee BioMed Central

Merkel cell polyomavirus large T antigen disrupts lysosome clustering by translocating human Vam6p from the cytoplasm to the nucleus

Merkel cell polyomavirus (MCV) has been recently described as the cause for most human Merkel cell carcinomas. MCV is similar to simian virus 40 (SV40) and encodes a nuclear large T (LT) oncoprotein that is usually mutated to eliminate viral replication among tumor-derived MCV. We identified the hVam6p cytoplasmic protein involved in lysosomal processing as a novel interactor with MCV LT but not SV40 LT. hVam6p binds through its clathrin heavy chain homology domain to a unique region of MCV LT adjacent to the retinoblastoma binding site. MCV LT translocates hVam6p to the nucleus, sequestering it from involvement in lysosomal trafficking. A naturally occurring, tumor-derived mutant LT (MCV350) lacking a nuclear localization signal binds hVam6p but fails to inhibit hVam6p-induced lysosomal clustering. MCV has evolved a novel mechanism to target hVam6p that may contribute to viral uncoating or egress through lysosomal processing during virus replication

Voids in massive neutrino cosmologies

Cosmic voids are a promising environment to characterize neutrino-induced effects on the large-scale distribution of matter in the universe. We perform a comprehensive numerical study of the statistical properties of voids, identified both in the matter and galaxy distributions, in massive and massless neutrino cosmologies. The matter density field is obtained by running several independent N-body simulations with cold dark matter and neutrino particles, while the galaxy catalogs are modeled by populating the dark matter halos in simulations via a halo occupation distribution (HOD) model to reproduce the clustering properties observed by the Sloan Digital Sky Survey (SDSS) II Data Release 7. We focus on the impact of massive neutrinos on the following void statistical properties: number density, ellipticities, two-point statistics, density and velocity profiles. Considering the matter density field, we find that voids in massive neutrino cosmologies are less evolved than those in the corresponding massless neutrinos case: there is a larger number of small voids and a smaller number of large ones, their profiles are less evacuated, and they present a lower wall at the edge. Moreover, the degeneracy between \u3c38 and \u3a9\u3bd is broken when looking at void properties. In terms of the galaxy density field, we find that differences among cosmologies are difficult to detect because of the small number of galaxy voids in the simulations. Differences are instead present when looking at the matter density and velocity profiles around these voids. \ua9 2015 IOP Publishing Ltd and Sissa Medialab srl