Publications by authors named "M Tigano"
The activation of IP receptor (IPR) Ca channels generates agonist-mediated Ca signals that are critical for the regulation of a wide range of biological processes. It is therefore surprising that CRISPR induced loss of all three IPR isoforms (TKO) in HEK293 and HeLa cell lines yields cells that can survive, grow and divide, albeit more slowly than wild-type cells. In an effort to understand the adaptive mechanisms involved, we have examined the activity of key Ca dependent transcription factors (NFAT, CREB and AP-1) and signaling pathways using luciferase-reporter assays, phosphoprotein immunoblots and whole genome transcriptomic studies.
View Article and Find Full Text PDFMitochondrial DNA (mtDNA)-encoded RNA molecules undergo extensive processing to generate mature RNA, including removal of spurious poly-A tails by phosphodiesterase12 (PDE12). A new study by Van Haute and colleagues (Van Haute et al, 2024) describes the first pathogenic variants in the human PDE12 gene. The 3 missense mutations that were identified each carry severe phenotypic consequences that correlate with the presence or not of residual PDE12 protein, show cell-type-specific adaptive responses, and specificity in the mtDNA-encoded electron transport chain subunits that are most affected.
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- Recent advancements in genetic manipulation have made it possible to create specific deletions in mitochondrial DNA (mtDNA) in human cells, which can help study diseases linked to these genetic changes.
- A method involving co-expression of end-joining machinery and targeted endonucleases was developed, showcasing effectiveness by generating clonal cell lines with a significant mtDNA deletion and varying levels of heteroplasmy.
- Research showed that when mtDNA deletion reached around 75%, it led to severe cellular dysfunction and identified distinct nuclear gene expression changes in response to mtDNA deletions, suggesting insights for potential therapies.
Although viruses subvert innate immune pathways for their replication, there is evidence they can also co-opt anti-viral responses for their benefit. The ubiquitous human pathogen, Herpes Simplex Virus-1 (HSV-1), encodes a protein (UL12.5) that induces the release of mitochondrial nucleic acid into the cytosol, which activates immune sensing pathways and reduces productive replication in non-neuronal cells.
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