Aging-US: UBB+1 reduces amyloid-β cytotoxicity by activation of autophagy
12-20-2021Aging-US published "UBB+1 reduces amyloid-β cytotoxicity by activation of autophagy in yeast" which reported that in their previous study, these authors found that yeast cells expressing UBB 1 at lower level display an increased resistance to cellular stresses under conditions of chronological aging.
In order to examine the molecular mechanisms behind, here they performed genome-wide transcriptional analyses and molecular/cellular biology assays. Furthermore, they introduced low UBB 1 expression to our humanized yeast AD models, that constitutively express Aβ42 and Aβ40 peptide, respectively.
The co-expression of UBB 1 with Aβ42 or Aβ40 peptide led to reduced intracellular Aβ levels, ameliorated viability, and increased chronological life span. In an autophagy deficient background strain , intracellular Aβ levels were not affected by UBB 1 expression. The findings offer insights for reducing intracellular Aβ toxicity via autophagy-dependent cellular pathways under low level of UBB 1 expression.
Dr. Dina Petranovic from The Chalmers University of Technology said, "Proteins are frequently misfolded during the lifetime of a cell, as a consequence of stochastic fluctuations of the structures, genomic mutations, oxidation or other different stress conditions."
Unlike the UBB, UBB 1 fails to ligate protein substrates or join polyubiquitin chains due to the absence of the C-terminal glycine residue, but like any other damaged protein recognized by the UPS system, it is readily ubiquitylated and degraded.
Figure 7. Low UBB+1 expression reduces Aβ42 and Aβ40 toxicity. (A) Survival of the Aβ42 and Aβ40 strains during stationary phase without or with low UBB+1 expression under wild type background. (B) Survival of the Aβ42 and Aβ40 strains during stationary phase without or with low UBB+1 expression under atg1Δ mutant background. Viability was determined by CFU counting. The data are shown as mean ± SD from biological duplicates.
Low levels of UBB 1 can be ubiquitinated and efficiently degraded by the UPS, whereas at high levels, the UPS fails to degrade UBB 1 and the accumulation of UBB 1 further induces functional impairment of the UPS.
Despite the UBB 1-induced UPS dysfunction, in some cases UBB 1 expression is protective by the induction of heat-shock proteins, which promote cellular resistance to oxidative stress.
To exploit the effects of UBB 1 expression on proteasome function and cellular viability, these authors recently developed two yeast models using constitutive expression of the human UBB 1, expressed at high and low levels.
The Petranovic Research Team concluded in their Aging-US Research Output that this study shows that low UBB 1 expression significantly increased the autophagy activity and thus induced intracellular degradation of Aβ, which increased cell fitness and survival.
This study shows that low UBB 1 expression significantly increased the autophagy activity and thus induced intracellular degradation of Aβ, which increased cell fitness and survival.
Full Text - https://www.aging-us.com/article/203681/text/
Correspondence to: Dina Petranovic email: dina.petranovic@chalmers.se
Keywords: UBB+1, autophagy, amyloid-β, Alzheimer’s disease, yeast