Debora Gentile
@tigem.it
Tigem
RESEARCH INTERESTS
Autophagy, selective autophagy, cancer, cancer stem cells, natural products, new pharmacological target
Scopus Publications
Scopus Publications
Anna Matveeva, Orla Watters, Ani Rukhadze, Niraj Khemka, Debora Gentile, Ivan Fernandez Perez, Irene Llorente-Folch, Cliona Farrell, Elide Lo Cacciato, Joshua Jackson,et al.
Informa UK Limited
OBJECTIVE
Sporadic and familial amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease that results in loss of motor neurons and, in some patients, associates with frontotemporal dementia (FTD). Apart from the accumulation of proteinaceous deposits, emerging literature indicates that aberrant mitochondrial bioenergetics may contribute to the onset and progression of ALS/FTD. Here we sought to investigate the pathophysiological signatures of mitochondrial dysfunction associated with ALS/FTD.
METHODS
By means of label-free mass spectrometry (MS) and mRNA sequencing (mRNA-seq), we report pre-symptomatic changes in the cortices of TDP-43 and FUS mutant mouse models. Using tissues from transgenic mouse models of mitochondrial diseases as a reference, we performed comparative analyses and extracted unique and common mitochondrial signatures that revealed neuroprotective compensatory mechanisms in response to early damage.
RESULTS
In this regard, upregulation of both Acyl-CoA Synthetase Long-Chain Family Member 3 (ACSL3) and mitochondrial tyrosyl-tRNA synthetase 2 (YARS2) were the most representative change in pre-symptomatic ALS/FTD tissues, suggesting that fatty acid beta-oxidation and mitochondrial protein translation are mechanisms of adaptation in response to ALS/FTD pathology.
CONCLUSIONS
Together, our unbiased integrative analyses unveil novel molecular components that may influence mitochondrial homeostasis in the earliest phase of ALS.
Debora Gentile, Marianna Esposito, and Paolo Grumati
Frontiers Media SA
Autophagy is an evolutionary conserved catabolic pathway that uses a unique double-membrane vesicle, called autophagosome, to sequester cytosolic components, deliver them to lysosomes and recycle amino-acids. Essentially, autophagy acts as a cellular cleaning system that maintains metabolic balance under basal conditions and helps to ensure nutrient viability under stress conditions. It is also an important quality control mechanism that removes misfolded or aggregated proteins and mediates the turnover of damaged and obsolete organelles. In this regard, the idea that autophagy is a non-selective bulk process is outdated. It is now widely accepted that forms of selective autophagy are responsible for metabolic rewiring in response to cellular demand. Given its importance, autophagy plays an essential role during tumorigenesis as it sustains malignant cellular growth by acting as a coping-mechanisms for intracellular and environmental stress that occurs during malignant transformation. Cancer development is accompanied by the formation of a peculiar tumor microenvironment that is mainly characterized by hypoxia (oxygen < 2%) and low nutrient availability. Such conditions challenge cancer cells that must adapt their metabolism to survive. Here we review the regulation of autophagy and selective autophagy by hypoxia and the crosstalk with other stress response mechanisms, such as UPR. Finally, we discuss the emerging role of ER-phagy in sustaining cellular remodeling and quality control during stress conditions that drive tumorigenesis.
Joshua Jackson, Lena Wischhof, Enzo Scifo, Anna Pellizzer, Yiru Wang, Antonia Piazzesi, Debora Gentile, Sana Siddig, Miriam Stork, Chris E. Hopkins,et al.
Elsevier BV
Debora Gentile, Laura Berliocchi, Rossella Russo, Giacinto Bagetta, and Maria Tiziana Corasaniti
Elsevier BV
Laura Berliocchi, Carlotta Chiappini, Annagrazia Adornetto, Debora Gentile, Silvia Cerri, Rossella Russo, Giacinto Bagetta, and Maria Tiziana Corasaniti
Elsevier BV