Study extends the understanding of the link between telomeres and mitochondria
An international team of researchers from Germany, France, Singapore, and Australia has uncovered how the ZBTB48 protein functions to regulate telomeres and mitochondria. Findings of the study, which appear online in EMBO reports, could deepen our understanding of ageing and carcinogenesis.
Telomeres are distinctive structures localized at the ends of chromosomes. They consist of repetitive nucleotide sequences, and their main functions are to protect chromosome ends from degradation and to maintain chromosome stability. Each time a cell divides, telomeres get shorter. When telomeres become too shorter, the cell stops replicating and eventually dies, which is associated with cellular ageing. However, cancer cells can keep replicating via various mechanisms that prevent telomere shortening. In addition to cancer, telomeres have also been implicated in other diseases, such as diabetes, cardiovascular disease, and autoimmune disease.
Mitochondria, which are membrane-bound organelles in eukaryotic organisms, function to produce energy for cells and regulate cellular metabolism. Metabolic disease research suggests a strong link between telomeres and mitochondrial metabolism. A better understanding of telomeres would help understand a wide range of health conditions. Therefore, a lot of efforts have been made to identify telomere-associated factors. One of the factors, the protein ZBTB48, was recently found to bind to extremely long telomeres and prevent them from growing further.
The present study, co-led by Dennis Kappei from the National University of Singapore, Falk Butter from the Institute of Molecular Biology gGmbH, and Frank Buchholz from the TU Dresden, revealed that ZBTB48 binds directly to telomeres and confirmed that the protein acts as a negative regulator of telomere length. Besides, the study discovered that ZBTB48 also acts as a transcriptional activator, which regulates the expression of a set of genes, including MTFP1. MTFP1, or called mitochondrial fission process 1, is a mitochondrial protein and is involved in mitochondrial dynamics. Collectively, these findings extend the understanding of the link between telomere and mitochondrial homeostasis.
Given that telomeres and mitochondria both play important roles in ageing, cancer, and many other health conditions, the study would have profound implications. Further research will focus on the function of ZBTB48 in ageing and carcinogenesis.
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