Rheb and mammalian target of rapamycin in mitochondrial homoeostasis.

Mitochondrial dysfunction has been associated with various diseases, such as cancer, myopathies, neurodegeneration and obesity. Mitochondrial homoeostasis is achieved by mechanisms that adapt the number of mitochondria to that required for energy production and for the supply of metabolic intermediates necessary to sustain cell growth. Simultaneously, mitochondrial quality control mechanisms are in place to remove malfunctioning mitochondria.

Mammalian target of rapamycin complex I (mTORC1) activity in ras homologue enriched in brain (Rheb)-deficient mouse embryonic fibroblasts.

The Ras-like GTPase Rheb has been identified as a crucial activator of mTORC1. Activation most likely requires a direct interaction between Rheb and mTOR, but the exact mechanism remains unclear. Using a panel of Rheb-deficient mouse embryonic fibroblasts (MEFs), we show that Rheb is indeed essential for the rapid increase of mTORC1 activity following stimulation with insulin or amino acids.

Rheb and Rags come together at the lysosome to activate mTORC1.

mTORC1 (mammalian target of rampamycin complex 1) is a highly conserved protein complex regulating cell growth and metabolism via its kinase mTOR (mammalian target of rapamycin). The activity of mTOR is under the control of various GTPases, of which Rheb and the Rags play a central role. The presence of amino acids is a strict requirement for mTORC1 activity.

Detection and characterization of two chimpanzee polyomavirus genotypes from different subspecies.

The complete nucleotide sequences of three chimpanzee polyomavirus genetic variants were determined. Phylogenetic analysis indicated that the viruses form two different genotypes of ChPyV. Comparison with other primate polyomaviruses revealed a putative agnogene, and an unusually long VP1 open reading frame.

Characterization of novel polyomaviruses from Bornean and Sumatran orang-utans.

Serological screening of sera from orang-utans demonstrated a high percentage of sera that cross-reacted with antigens of the polyomavirus (PyV) simian virus 40. Analysis of archival DNA samples from 71 Bornean and eight Sumatran orang-utans with a broad-spectrum PCR assay resulted in the detection of PyV infections in 11 animals from both species. Sequence analysis of the amplicons revealed considerable differences between the PyVs from Bornean and Sumatran orang-utans.