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Protein aggregation, and in particular amyloid formation, has historically been considered as an aberrant, irreversible process, and it has been commonly associated with several devastating pathologies, such as Alzheimer’s disease, Parkinson’s disease or amyotrophic lateral sclerosis. However, recent insights challenge this view, and provide evidence that protein aggregation not only can be a regulated, reversible process, but can also fulfil essential physiological functions. Indeed, reversible protein aggregates have been implicated in several cellular processes, ranging from peptide hormone storage to long-term memory formation. Yet, the regulatory mechanisms underlying reversible, functional aggregation, as well as the exact physiological implications of these processes, are still poorly understood. The goal of this thesis is to fill this gap, and elucidate the regulatory mechanisms and physiological implications underlying stress-induced reversible protein aggregation. In particular, by combining genetic, biochemical and cell biological approaches, I aimed to unravel the structure, function and regulation of stress-induced reversible aggregates of yeast pyruvate kinase (Cdc19) and its human homolog (PKM2). This essential glycolytic enzyme is a pivotal and evolutionarily conserved regulator of cellular metabolism, energy homeostasis and cell growth. This study reveals that pyruvate kinase forms reversible aggregates upon stress, both in yeast and human cells. The aggregation of Cdc19 depends on an aggregation-prone low-complexity region (LCR), also called “amyloid core”, and is controlled by several regulatory mechanisms involving protonation, phosphorylation, metabolite binding and changes in oligomerization state. Cdc19 aggregates localize to stress granules, have an amyloid structure and are inactive. By reversibly aggregating Cdc19, cells arrest glycolysis and protect Cdc19 from stress-induced degradation. This allows them to rapidly restore ATP production and efficiently disassemble stress granule after stress release. Thus, we propose that the formation of reversible Cdc19 amyloids couples cellular metabolism with stress granule dynamics and is essential for cell cycle restart after the cessation of stress. Similarly, PKM2 aggregates in vivo by the virtue of an amyloid core and forms inactive amyloid aggregates in vitro. These data suggest that the mechanisms and functions of pyruvate kinase aggregation are conserved from yeast to human. In summary, this thesis demonstrates that protein aggregation can be an adaptive cellular response. Moreover, it unravels conserved and potentially widespread mechanisms regulating amyloid formation and disassembly. Understanding these principles not only sheds light onto an essential physiological process, but could also have important implications for developing novel strategies to treat amyloid-related diseases.