Arabidopsis HIPP proteins regulate endoplasmic reticulum-associated degradation of CKX proteins and cytokinin responses.

Eukaryotic organisms are equipped with quality-control mechanisms that survey protein folding in the endoplasmic reticulum (ER) and remove non-native proteins by ER-associated degradation (ERAD). Recent research has shown that cytokinin-degrading CKX proteins are subjected to ERAD during plant development. The mechanisms of plant ERAD, including the export of substrate proteins from the ER, are not fully understood and the molecular components involved in the ERAD of CKX are unknown. We show that heavy metal-associated isoprenylated plant proteins (HIPP) interact specifically with CKX proteins synthesized in the ER and processed by ERAD. CKX-HIPP protein complexes were detected at the ER as well as in the cytosol, suggesting that the complexes involve retrotranslocated CKX protein species. Altered CKX levels in HIPP-overexpressing and higher-order hipp mutant plants suggest that the studied HIPP proteins control the ERAD of CKX. Deregulation of CKX proteins caused corresponding changes in the cytokinin signaling activity and triggered typical morphological cytokinin responses. Notably, transcriptional repression of HIPP genes by cytokinin indicates a feedback regulatory mechanism of cytokinin homeostasis and signaling responses. Moreover, the loss of HIPP genes constitutively activates the unfolded protein response and compromises the ER stress tolerance, supporting the conclusion that HIPPs represent novel functional components of plant ERAD.

Liquid-liquid phase separation in human health and diseases

Emerging evidence suggests that liquid-liquid phase separation(LLPS)represents a vital and ubiquitous phenomenon underlying the formation of membraneless organelles in eukaryotic cells(also known as biomolecular condensates or droplets).Recent studies have revealed evidences that indicate that LLPS plays a vital role in human health and diseases.In this review,we describe our current understanding of LLPS and summarize its physiological functions.We further describe the role of LLPS in the development of human diseases.Additionally,we review the recently developed methods for studying LLPS.Although LLPS research is in its infancy-but is fast-growing-it is clear that LLPS plays an essential role in the development of pathophysiological conditions.This highlights the need for an overview of the recent advances in the field to translate our current knowledge regarding LLPS into therapeutic discoveries.

Migratory flight imposes oxidative stress in bats

Many animal species migrate over long distances, but the physiological challenges of migration are poorly understood. It has recently been suggested that increased molecular oxidative damage might be one important challenge for migratory animals. We tested the hypothesis that autumn migration imposes an oxidative challenge to bats by comparing values of 4 blood-based markers of oxidative status (oxidative damage and both enzymatic and nonenzymatic antioxidants) between Nathusius' bats Pipistrellus nathusii that were caught during migration flights with those measured in conspecifics after resting for 18 or 24 h. Experiments were carried out at Pape Ornithological Station in Pape (Latvia) in 2016 and 2017. Our results show that flying bats have a blood oxidative status different from that of resting bats due to higher oxidative damage and different expression of both non enzymatic and enzymatic antioxidants (glutathione peroxidase). The differences in oxidative status markers varied betwee n sampli ng years and were in depende nt from in dividual body con dition or sex. Our work provides evidence that migratory flight might impose acute oxidative stress to bats and that resting helps animals to recover from oxidative damage accrued en route. Our data suggest that migrating bats and birds might share similar strategies of mitigating and recovering from oxidative stress.