Aggregation of damaged or misfolded proteins is a protective mechanism against proteotoxic stress, abnormalities of which underlie many aging-related diseases. Here, we show that in asymmetrically dividing yeast cells, aggregation of cytosolic misfolded proteins does not occur spontaneously but requires new polypeptide synthesis and is restricted to the surface of ER, which harbors the majority of active translation sites. Protein aggregates formed on ER are frequently also associated with or are later captured by mitochondria, greatly constraining aggregate mobility. During mitosis, aggregates are tethered to well-anchored maternal mitochondria, whereas mitochondria acquired by the bud are largely free of aggregates. Disruption of aggregate-mitochondria association resulted in increased mobility and leakage of mother-accumulated aggregates into the bud. Cells with advanced replicative age exhibit gradual decline of aggregates-mitochondria association, likely contributing to their diminished ability to rejuvenate through asymmetric cell division. Display omitted •Aggregation of misfolded cytosolic proteins requires active translation•Aggregation is initiated by newly synthesized polypeptides on the surface of ER•ER-associated aggregation sites are frequently bound or captured by mitochondria•Mitochondria control the dynamics and asymmetric segregation of aggregates Aggregation of cytosolic misfolded proteins requires new polypeptide synthesis, is restricted to the surface of ER, and is later captured by mitochondria, enabling asymmetric inheritance of protein aggregates during yeast cell division.