High and stable ATP levels prevent aberrant intracellular protein aggregation in yeast
Year: 2022
Type: article
Abstract: Adenosine triphosphate (ATP) at millimolar levels has recently been implicated in the solubilization of cellular proteins. However, the significance of this high ATP level under physiological conditions and the mechanisms that maintain ATP remain unclear. We herein demonstrated that AMP-activated protein kinase (AMPK) and adenylate kinase (ADK) cooperated to maintain cellular ATP levels regardless of glucose levels. Single-cell imaging of ATP-reduced yeast mutants revealed that ATP levels in these mutants underwent stochastic and transient depletion, which promoted the cytotoxic aggregation of endogenous proteins and pathogenic proteins, such as huntingtin and α-synuclein. Moreover, pharmacological elevations in ATP levels in an ATP-reduced mutant prevented the accumulation of α-synuclein aggregates and its cytotoxicity. The present study demonstrates that cellular ATP homeostasis ensures proteostasis and revealed that suppressing the high volatility of cellular ATP levels prevented cytotoxic protein aggregation, implying that AMPK and ADK are important factors that prevent proteinopathies, such as neurodegenerative diseases.
Source: eLife
DOI: 10.7554/elife.67659
Authors: Masak Takaine, Hiromi Imamura, Satoshi Yoshida
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: Selective inheritance of mitochondria from mother cells into spores in fission yeast, A mechanism that switches the signaling specificity of Rho1 GTPase, Elucidation of the mechanism by which the de novo purine synthesis enzyme PPAT forms intracellular granules and its physiological significance, Elucidating mechanisms by which high levels of ATP prevent accumulation of aberrant protein aggregation
OpenAlex ID: W4224215175