A virtuous cycle operated by ERp44 and ERGIC-53 guarantees proteostasis in the early secretory compartment.

The composition of the secretome depends on the combined action of cargo receptors that facilitate protein transport and sequential checkpoints that restrict it to native conformers. Acting after endoplasmic reticulum (ER)-resident chaperones, ERp44 retrieves its clients from downstream compartments. To guarantee efficient quality control, ERp44 should exit the ER as rapidly as its clients, or more.

PINK1 and Parkin: The odd couple.

In 2004, PINK1 was established as a gene linked to early onset of autosomal recessive juvenile Parkinsonism. Since then, tremendous efforts allowed involving the gene product in diverse events but with a strong focus on its partnership with the protein Parkin for the degradation of damaged mitochondria through mitophagy. Yet, it is now clear that the importance of PINK1 encompasses a wider spectrum of intracellular processes.

Redox crosstalk at endoplasmic reticulum (ER) membrane contact sites (MCS) uses toxic waste to deliver messages.

Many cellular redox reactions housed within mitochondria, peroxisomes and the endoplasmic reticulum (ER) generate hydrogen peroxide (HO) and other reactive oxygen species (ROS). The contribution of each organelle to the total cellular ROS production is considerable, but varies between cell types and also over time. Redox-regulatory enzymes are thought to assemble at a "redox triangle" formed by mitochondria, peroxisomes and the ER, assembling "redoxosomes" that sense ROS accumulations and redox imbalances.

Regulation of Calcium Fluxes by GPX8, a Type-II Transmembrane Peroxidase Enriched at the Mitochondria-Associated Endoplasmic Reticulum Membrane.

Unlabelled: Glutathione peroxidases (GPXs) are enzymes that are present in almost all organisms with the primary function of limiting peroxide accumulation. In mammals, two of the eight members (GPX7 and GPX8) reside in the endoplasmic reticulum (ER). A peculiar feature of GPX8 is the concomitant presence of a conserved N-terminal transmembrane domain (TMD) and a C-terminal KDEL-like motif for ER localization.

A dynamic study of protein secretion and aggregation in the secretory pathway.

Precise coordination of protein biogenesis, traffic and homeostasis within the early secretory compartment (ESC) is key for cell physiology. As a consequence, disturbances in these processes underlie many genetic and chronic diseases. Dynamic imaging methods are needed to follow the fate of cargo proteins and their interactions with resident enzymes and folding assistants.