UBB+1-induced activation of autophagy reduces cytotoxicity of amyloid-β in yeast

UBB+1 is a mutated version of ubiquitin B caused by a transcriptional frameshift. The accumulation of UBB+1, has been linked to ubiquitin-proteasome system (UPS) dysfunction and neurodegeneration. Alzheimer’s disease (AD) is the most common form of neurodegeneration and accumulation of amyloid β (Aβ) in the brain is a prominent neuropathological feature of AD. In our previous study, we found that low expression of UBB+1 could protect cells against several stresses during chronological aging. Here, we applied the genome-wide expression analyses and found that low UBB+1 expression activated the autophagy pathway. Low UBB+1 expression was shown to upregulate vacuolar activity and promote transport of the ATG8p (autophagic marker) to the vacuole. To further study the effects, we expressed low level of UBB+1 in our humanized yeast Aβ models with the expression of either Aβ42 or Aβ40. Interestingly, the co-expression of UBB+1 with Aβ42 or Aβ40 showed a reduction of intracellular Aβ levels and increased chronological life span. In the autophagy deficient mutant background (atg1∆), the intracellular Aβ levels were not affected by UBB+1 expression. Our findings suggest a mechanism of UBB+1 action in reducing intracellular levels of Aβ. The goal of the present study is to evaluate the impact of low expression level of UBB+1 on yeast physiology and transcriptome profiles following the growth phases. Saccharomyces cerevisiae expressing empty plasmid (control strain) and p413 TEF UBB+1 plasmid (LUBB+1 strain) respectively was cultivated in shake flask at 30℃. Samples were taken from duplicate cultures during exponential phase (EX) and day 6 (D6).