Publications by authors named "M DEPAOLI"
Cancer cells voraciously consume nutrients to support their growth, exposing metabolic vulnerabilities that can be therapeutically exploited. Here, we show in hepatocellular carcinoma (HCC) cells, xenografts, and patient-derived organoids that fasting improves sorafenib efficacy and acts synergistically to sensitize sorafenib-resistant HCC. Mechanistically, sorafenib acts noncanonically as an inhibitor of mitochondrial respiration, causing resistant cells to depend on glycolysis for survival.
View Article and Find Full Text PDFThe metabolic activity of cells is interrelated with cell signaling, functions, and fate. Uncontrolled cancer cell proliferation requires metabolic adaptations. Research focusing on understanding the characteristics of cell metabolism is crucial for the development of novel diagnostic and therapeutic strategies.
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- Researchers developed new Ca biosensors specifically targeted to the intermembrane space and cristae lumen of mitochondria, allowing for enhanced visualization of calcium levels in different mitochondrial compartments.
- Functional studies showed that knocking down certain proteins, like MCU and EMRE, affected Ca levels distinctly in the cristae lumen but not in the intermembrane space, indicating specific pathways for Ca transfer.
- The newly designed biosensors provide high-resolution imaging capabilities for studying calcium signaling in mitochondria, which could help in understanding its role in various physiological and pathological conditions.
Background/aims: In our recent work, the importance of GSK3β-mediated phosphorylation of presenilin-1 as crucial process to establish a Ca leak in the endoplasmic reticulum and, subsequently, the pre-activation of resting mitochondrial activity in β-cells was demonstrated. The present work is a follow-up and reveals the importance of GSK3β-phosphorylated presenilin-1 for responsiveness of pancreatic islets and β-cells to elevated glucose in terms of cytosolic Ca spiking and insulin secretion.
Methods: Freshly isolated pancreatic islets and the two pancreatic β-cell lines INS-1 and MIN-6 were used.
The interplay of metabolic and signaling processes is prerequisite for the functionality of cells. Any disturbances may have severe consequences, resulting in the development of diseases. However, the complex coordination of metabolism and signaling events makes it difficult to decipher the link between molecular irregularities and pathogenesis.
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