Barbara Stiller

Highlights • CMA and eMI activities are upregulated in response to failure of each other • A selective part of the CMA subproteome is rerouted to eMI upon CMA blockage • Bag6 is required for substrate internalization by eMI • Starvation inhibits eMI through changes in Bag6 dynamics in late endosomes Summary Chaperone-mediated autophagy (CMA) and endosomal microautophagy (eMI) are pathways for selective degradation of cytosolic proteins in lysosomes and late endosomes, respectively.

Recent breakthroughs in genomic research have clarified that genetic and environmental factors jointly contribute to the aetiology of many cardiovascular diseases. The identification of genes or, even better, genetically driven disease mechanisms involved in this process are crucial steps for improving risk prediction and developing better treatments.

Hsc-70 (HSPA8) is a cytosolic molecular chaperone, which plays a central role in cellular proteostasis including quality control during protein refolding and regulation of protein degradation. Hsc-70 is pivotal to the process of macro-autophagy, chaperone-mediated autophagy and endosomal microautophagy. The latter requires hsc-70 interaction with negatively charged phosphatidylserine (PS) at the endosomal limiting membrane.