Aneuploidy-induced proteostasis disruption impairsmitochondrial functions and mediates aggregation ofmitochondrial precursor proteins through SQSTM1/p62.

According to a preprint abstract, aneuploidy, or abnormal chromosomal content, has a significant impact on cellular physiology. Even a gain of a single chromosome disrupts proteostasis, leading to the accumulation of cytosolic bodies and altered proteasomal and lysosomal activity. The study found that aneuploid cells have an enrichment of mitochondrial proteins within the cytosolic p62 interactome, leading to mitochondrial defects such as reduced oxygen consumption and reduced mitochondrial DNA abundance. Additionally, the study suggests that proteotoxic stress induced by chromosome gains leads to the sequestration of mitochondrial precursor proteins into cytosolic p62-bodies, compromising mitochondrial function. This research has not yet undergone peer review. [Extracted from the article]