The efficiency, divergence, and specificity of virtually all intracellular metabolic and signalling pathways largely depend on their compartmentalized organization. A corollary of the requirement of compartmentalization is the dynamic structural partition of the intracellular space by endomembrane systems. A branch of these membranes communicate with the extracellular space through the endo- and exocytotic processes. Others, like the mitochondrial and endoplasmic reticulum networks accomplish a further role, being fundamental for the maintenance of cellular energy balance and for determination of cell fate under stress conditions. Recent structural and functional studies revealed that the interaction of these networks and the connectivity state of mitochondria controls metabolic flow, protein transport, intracellular Ca2+ signalling, and cell death. Moreover, reflecting the fact that the above processes are accomplished in a microdomain between collaborating organelle membranes, the existence of macromolecular complexes at their contact sites have also been revealed. Being not only assistants of nascent protein folding, chaperones are proposed to participate in assembling and maintaining the function of the above complexes. In this chapter we discuss recently found examples of such an assembly of protein interactions driven by chaperone proteins, and their role in regulating physiological and pathological processes.