How Chromosome Imbalances Affect Mitochondrial Function in Cancer Cells

Researchers at the University of Kaiserslautern-Landau have uncovered a significant link between chromosome abnormalities and mitochondrial dysfunction in cancer cells. Abnormal chromosome numbers, known as aneuploidy, are common in many cancers and genetic syndromes like Down syndrome. These imbalances cause protein production imbalances within cells, leading to various cellular stresses.

In their recent study, scientists used cell lines derived from colorectal cancer cells (HCT116) that were genetically modified to carry extra copies of certain chromosomes. They observed that these aneuploid cells tend to develop protein aggregates containing sequestosome 1 (SQSTM1 or p62), a receptor involved in recycling damaged proteins and organelles. The amount of this protein increased proportionally with the number of extra chromosomes.

A critical finding was that these cells showed altered mitochondrial structure and impaired function. The sequestration of mitochondrial precursor proteins into p62-positive aggregates hindered their proper import into mitochondria, disrupting energy production and cellular metabolism. This discovery highlights a direct connection between genomic alterations, proteotoxic stress, and mitochondrial health.

Interestingly, despite the stress from chromosomal imbalance, cancer cells often tolerate proteome disruptions better than normal cells. Researchers suggest that cancer cells may adapt their mitochondrial metabolism to survive under such conditions, which could also contribute to their resistance to certain drugs.

These insights could have important therapeutic implications, as targeting mitochondrial alterations or the protein aggregation pathways may offer new avenues for cancer treatment. The study emphasizes the importance of understanding the molecular effects of chromosomal abnormalities in developing more effective therapies.

This research was published in Nature Communications. For more details, visit here. Source: https://medicalxpress.com/news/2025-06-chromosome-imbalances-disrupt-mitochondrial-function.html