Metabolism produces energy and molecules required for growth and development. However, some fundamental reactions such as histone demethylations or the one-carbon cycle can also generate surplus formaldehyde, which reaches surprisingly high micromolar blood levels. This ‘endogenous’ formaldehyde is very reactive and can damage proteins and DNA resulting in lethal damage. Fortunately, cells evolved two protective barriers: the formaldehyde-detoxifying enzyme alcohol dehydrogenase 5 (ADH5) and the Fanconi Anemia DNA repair pathway. The simultaneous inactivation of these two systems leads to hematopoietic stem cell attrition, kidney and liver dysfunction, and development of cancer in mice. Remarkably, cancer cells express robust formaldehyde-detoxifying systems opening innovative therapeutic possibilities.
In this seminar, I will describe our recent research which has uncovered novel cellular targets of cytotoxic formaldehyde and an unforeseen pathway that limits the toxicity of this ubiquitous metabolite.
Extraordinary Plenary Seminar
Data i hora d'inici: 05/03/2020, 12.00h
Data i hora de fi: 05/03/2020, 13.30h
Organitzador: IRB - Institut de Recerca Biomèdica
Lloc: Edifici Clúster Laboratoris, Aula Félix Serratosa
Host: Ángel R. Nebreda, PhD - IRB Barcelona