The DFG-funded Research Unit FOR2625 “Mechanisms of Lysosomal Homeostasis” is an inter-disciplinary network comprising internationally recognized senior and junior scientists from Germany and The Netherlands with a broad expertise in research on lysosomes, autophagy and lysosomal diseases. Funded in 2017, the consortium aims at elucidating the molecular mechanisms of maintaining lysosomal homeostasis and the adaptive regulatory mechanisms to compensate lysosomal dysfunctions.

Lysosomes serve as final degradative compartments in eukaryotic cells and degrade intra- and extracellular material delivered by endocytosis, phagocytosis and autophagy. Degradation is achieved by the concerted action of 60 luminal acid hydrolases and more than 200 integral membrane proteins involved in luminal acidification and ion composition, translocation of degradation products to the cytosol and in contact and fusion with other organelles. Although lysosomal protein defects have been known to be the cause for a plethora of different rare diseases for a long time, only in recent years the view on lysosomes as a purely degradative compartment has changed towards lysosomes as a central player in adaptive responses to metabolic, developmental and environmental cues by lysosome-nucleus signaling processes.

The FOR2625 research program strongly benefits from the wide spread expertises of its members by synergistic collaborations and focusses in the research unit’s 2nd funding period on following three key objectives:

(1) protein machineries involved in biosynthetic and endocytic transport to and from lysosomes and in lysosomal signaling affect their function and biogenesis, including the analysis of protein ubiquitination, phosphorylation and acetylation

(2) analysis of lysosome-organelle contact sites and the machinery for autophagosome-lysosome fusion and lysosome reformation

(3) mechanisms controlling lysosome motility and positioning.

Advancing our knowledge of the molecular mechanisms underlying the various functions of lysosomes in the maintenance of cell and organismal homeostasis is a prerequisite to understand the pathomechanisms causing lysosome-related diseases and for the development of novel therapeutic strategies.

FOR2625 is funded by the German Research Foundation since October 2017, the second funding period of the consortium was approved in September 2020 with a duration of another 3 years and a cost-neutral extension until December 2024.