Virus-like particles (VLPs) are the products of endogenous retroelements in the yeast, Saccharomyces cerevisiae. Retroelement propagation is linked to aging, but the mechanisms of their effects are still emerging. We show that VLPs are markedly enriched in sites of protein aggregation. RNAi (RNA interference)-mediated silencing of retroelement expression perturbed aggregate sequestration to mitochondria, reduced overall protein aggregation, mitigated toxicity of a Huntington’s disease model, and expanded replicative lifespan in a partially Hsp104-dependent manner. These findings link VLPs to a toxic accumulation of protein aggregates and raise the possibility that they might negatively influence neurological disease progression. Our findings therefore reveal consequences of VLP expression and further our understanding of how aging, age-related diseases, and protein quality control function are linked.
A major consequence of aging and stress, in yeast to humans, is an increased accumulation of protein aggregates at distinct sites within the cells. Using genetic screens, immunoelectron microscopy, and three-dimensional modeling in our efforts to elucidate the importance of aggregate annexation, we found that most aggregates in yeast accumulate near the surface of mitochondria. Further, we show that virus-like particles (VLPs), which are part of the retrotransposition cycle of Ty elements, are markedly enriched in these sites of protein aggregation. RNA interference-mediated silencing of Ty expression perturbed aggregate sequestration to mitochondria, reduced overall protein aggregation, mitigated toxicity of a Huntington’s disease model, and expanded the replicative lifespan of yeast in a partially Hsp104-dependent manner. The results are in line with recent data demonstrating that VLPs might act as aging factors in mammals, including humans, and extend these findings by linking VLPs to a toxic accumulation of protein aggregates and raising the possibility that they might negatively influence neurological disease progression.