Tor Directly Controls the Atg1 Kinase Complex To Regulate Autophagy▿

Autophagy is a bulk proteolytic process that is indispensable for cell survival during starvation. Autophagy is induced by nutrient deprivation via inactivation of the rapamycin-sensitive Tor complex1 (TORC1), a protein kinase complex regulating cell growth in response to nutrient conditions. However, the mechanism by which TORC1 controls autophagy and the direct target of TORC1 activity remain unclear. Atg13 is an essential regulatory component of autophagy upstream of the Atg1 kinase complex, and here we show that yeast TORC1 directly phosphorylates Atg13 at multiple Ser residues. Additionally, expression of an unphosphorylatable Atg13 mutant bypasses the TORC1 pathway to induce autophagy through activation of Atg1 in cells growing under nutrient-rich conditions. Our findings suggest that the direct control of the Atg1 complex by TORC1 induces autophagy

Clinical studies of 20-year graft survivals of kidney transplantations

【Objective】Good long-term kidney graft function and graft survival depend on multiple factors. This study aimed to assess the impact of donor and recipient clinical factors on 20-year graft survival after kidney transplantation (KT). 【Material and Methods】From 1987-1994, twenty-five KTs (14 living and 11 deceased donors) were performed at Ryukyu University Hospital, and 24 of these cases were followed for more than 20 years after the KTs and reviewed. Ten patients had 20 years of graft survival, and 14 experienced graft failure for some reason within 20 years after KTs. Retrospective analyses were performed to elucidate the difference in donor and recipient factors among these patients. 【Results】The death censored graft survival rates at 5, 10, 15, and 20 years were 92.0%, 83.0%, 67.0%, and 67.0% in living-donor KTs and 73.0%, 62.0%, 62.0%, and 31.0% in deceased-donor KTs, respectively. The overall graft survival rates at 5, 10, 15, and 20 years were 85.0%, 77.0%, 62.0%, and 54.0% in living-donor KTs and 63.0%, 55.0%, 45.0%, and 27.0% in deceased-donor KTs, respectively. Comparison of clinical factors between the ≥ 20-year graft survivor group (10 cases) and <20-year graft survivor group (14 cases) revealed no differences in, for example, recipient age, duration of dialysis, donor age, donor type, number of human leukocyte antigen mismatches, and occurrence of acute rejections within 1 year of KTs. However, among 13 cases of living-donor KTs, the overall graft survivals after KTs from donors older than 50 years were worse than those after KTs from donors younger than 50 years. Also, the death-censored graft survivals after KTs from donors older than 60 years were worse than those after KTs from donors younger than 60 years. Moreover, graft survivals after KTs from maternal donors were worse than those after KTs from nonmaternal living donors, and there were no 20-year graft survivors after KTs from maternal donors. 【Conclusion】Our results suggest that the principal risk factors associated with <20-year graft survival after living-donor KTs are the presence of donors older than 50 or 60 years and a maternal donor