A conserved mechanism regulates reversible amyloids via pH-sensing regions [article]

Gea Cereghetti, Vera Maria Kissling, Lisa Maria Koch, Alexandra Arm, Pavel Afanasyev, Miriam Linsenmeier, Cedric Eichmann, Jiangtao Zhou, Yiping Cao, Dorota Maria Pfizenmaier, Sonja Kroschwald, Thomas Wiegand (+6 others)
2022 bioRxiv   pre-print
Amyloids were long viewed as irreversible, pathological aggregates, often associated with neurodegenerative diseases. However, recent insights challenge this view, providing evidence that reversible amyloids can form upon stress conditions and fulfil crucial cellular functions. Yet, the molecular mechanisms regulating functional amyloids and the differences to their pathological counterparts remain poorly understood. Here we investigate the conserved principles of amyloid reversibility by
more » ... ng the essential metabolic enzyme pyruvate kinase (PK) in yeast and human cells. We demonstrate that PK forms stress-dependent reversible amyloids through a pH-sensitive amyloid core. Stress-induced cytosolic acidification promotes aggregate formation via protonation of specific glutamate (in yeast) or histidine (in human) residues within the amyloid core. Our work thus unravels a conserved and potentially widespread mechanism underlying amyloid functionality and reversibility, fine-tuned to the respective physiological cellular pH range.
doi:10.1101/2022.03.21.484600 fatcat:t6zzn7gtinfmlbfqtsdz5v6gsq