New thesis: The interplay between mitochondria-endoplasmic reticulum contacts and Alzheimer’s disease

Hi Nuno Leal, PhD-student at the Division of Neurogeriatrics. On 26 April you will defend your thesis ”The interplay between mitochondria-endoplasmic reticulum contacts and Alzheimer’s disease”, what's the main focus of the thesis?

The main focus on my thesis is to study the interplay between mitochondria-endoplasmic reticulum (ER) contact sites (MERCS) and Alzheimer’s disease (AD). ER and mitochondria are two essential organelles in the cell that are, respectively, responsible for protein and energy generation. It is known that in AD, the interactions between these two organelles are increased but it remains unknown the reason why. In this thesis I tried to elucidate the connection between MERCS, Aβ metabolism and cell homeostasis (autophagosome formation and mitochondrial function).

Which are the most important results?

In this thesis we show an increase of number of MERCS in human brain biopsies of demented patients and in different AD models with increased levels of amyloid-β peptide, one of the hallmark of the pathology. We also showed that this increased of MERCS led to alterations in mitochondrial ultrastructure and autophagossome formation. Furthermore, we also discovered that TOM70 is involved in the modulation of calcium shuttling from ER to mitochondria.

How can this new knowledge contribute to the improvement of people’s health?

AD was first discovered more than 100 years ago but still there are no drugs that affect the ongoing neurodegenerative process which could be related with the fact that the molecular mechanism behind the pathology are still not completely understood. With the new data generated in this thesis we show, for the first time, that the contacts between ER and mitochondria can influence Aβ levels and vice-versa, showing that the metabolism of this protein and this subcellular region of the cell are intrinsically connected.

What´s in the future for you? Will you keep on conducting research?

Currently I am looking for postdoc positions, mostly outside of Europe. My plan is to join a lab where I can learn more about cellular mechanisms connected with cell metabolism and how these alterations alter neurological disorders.