The complete mtDNA sequences from the uncloned "founder" HeLa cells and from five sublines have been determined. These sequences all carry a common "core" of 38 single basepair alterations relative to the revised Cambridge Reference Sequence (CRS). The HeLa mitochondrial genome is of African descent and it is a member of the African L3 haplogroup. The sequence of the HeLa mtDNA resolves the uncertainty surrounding the mosaic composition of the original CRS for human mtDNA. Most importantly, we detected a total of eight polymorphisms that have arisen in the mtDNA coding region of different HeLa sublines. These observations suggest that HeLa mtDNA has a high rate of sequence divergence, relative to the phylogenetically-derived divergence rate for mtDNAs in the human population, which results from a relaxation of negative selection against the fixation of deleterious mutations. Furthermore, this high frequency of polymorphisms in HeLa mtDNA may reflect a process similar to the accumulation of somatic mtDNA mutations in human cancers. Preliminary analysis of single-cell derived subclone lines revealed the occurrence of another polymorphism and provided evidence for a large number of mtDNA segregation units.

Download full-text PDF

Source
http://dx.doi.org/10.1016/s0027-5107(01)00304-9DOI Listing

Publication Analysis

Top Keywords

hela mtdna
12
mtdna
9
high frequency
8
polymorphisms hela
8
hela
7
frequency mtdna
4
mtdna polymorphisms
4
hela cell
4
cell sublines
4
sublines complete
4

Similar Publications

The 40S ribosomal subunit recycling pathway is an integral link in the cellular quality control network, occurring after translational errors have been corrected by the ribosome-associated quality control (RQC) machinery. Despite our understanding of its role, the impact of translation quality control on cellular metabolism remains poorly understood. Here, we reveal a conserved role of the 40S ribosomal subunit recycling (USP10-G3BP1) complex in regulating mitochondrial dynamics and function.

View Article and Find Full Text PDF

The cytotoxic mechanisms of thymidylate synthase inhibitors, such as the multitarget antifolate pemetrexed, are not yet fully understood. Emerging evidence indicates that combining pemetrexed with histone deacetylase inhibitors (HDACi) may enhance therapeutic efficacy in non-small cell lung cancer (NSCLC). To explore this further, A549 NSCLC cells were treated with various combinations of pemetrexed and the HDACi MS275 (Entinostat), and subsequently assessed for cell viability, cell cycle changes, and genotoxic markers.

View Article and Find Full Text PDF

Triphenylphosphine-modified cyclometalated iridium complexes as mitochondria-targeting anticancer agents with enhanced selectivity.

Bioorg Chem

February 2025

Key Laboratory of Life-Organic Analysis of Shandong Province, Key Laboratory of Green Natural Products and Pharmaceutical Intermediates in Colleges and Universities of Shandong Province, School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165 PR China. Electronic address:

This study presents the development and evaluation of triphenylphosphine-modified cyclometalated iridium complexes as selective anticancer agents targeting mitochondria. By leveraging the mitochondrial localization capability of the triphenylphosphine group, these complexes displayed promising cytotoxicity in the micromolar range (3.12-7.

View Article and Find Full Text PDF

Triphenylphosphine-Modified Iridium, Rhodium, and Ruthenium Complexes to Achieve Enhanced Anticancer Selectivity by Targeting Mitochondria.

Inorg Chem

December 2024

Key Laboratory of Life-Organic Analysis of Shandong Province, Key Laboratory of Green Natural Products and Pharmaceutical Intermediates in Colleges and Universities of Shandong Province, School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, P. R. China.

The incorporation of an organelle-targeting moiety into compounds has proven to be an effective strategy in the development of targeted anticancer drugs. We herein report the synthesis, characterization, and biological evaluation of novel triphenylphosphine-modified half-sandwich iridium, rhodium, and ruthenium complexes. The primary goal was to enhance anticancer selectivity through mitochondrial targeting.

View Article and Find Full Text PDF
Article Synopsis
  • Irinotecan (CPT-11) is a chemotherapy drug that can harm healthy cells while treating cancer, while Nimotuzumab (NmAb) is a monoclonal antibody that targets the epidermal growth factor receptor (EGFR) in cancers with EGFR overexpression.
  • This study examines how the combination of CPT-11 and NmAb affects HeLa cervical cancer cells, finding that the combination leads to more cell death and apoptosis compared to either treatment alone.
  • The combined treatment increases levels of reactive oxygen species and activates key proteins involved in cell stress and death, suggesting that NmAb enhances the cancer-fighting effects of CPT-11 and could improve treatment for cervical cancer in humans.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!