Cellular mechanisms to counteract reactive aldehydes generated from fundamental metabolism: The formaldehyde paradigm.
Speaker: Dr. Lucas B. Pontel. IBioBA - MPSP. Instituto de Investigación en Biomedicina de Buenos Aires – CONICET – Partner Institute of the Max Planck Society. Buenos Aires, Argentina
Organizers: IRB Barcelona
Date: Thursday, 05 March 2020, 12.00h
Place: F. Serratosa. Parc Cientific de Barcelona
Host: Ángel R. Nebreda, PhD - IRB Barcelona
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 BioMed Seminar