Elisa Motori

Institute of Biochemistry, CMMC

Neuronal Stress Responses, Resilience and Regeneration

We are interested in understanding how mitochondrial metabolism regulates neuronal responses in disease models.

Research Focus

In our increasingly ageing society, neurodegenerative diseases are posing a major burden. A growing body of evidence has linked alterations in metabolism and mitochondrial function to some of the most devastating forms of neurodegeneration, including Parkinson´s disease, cerebellar ataxias and peripheral neuropathies. However, despite the urge to find strategies to prevent or arrest neurodegeneration, our understanding of the precise events underlying neuronal death caused by mitochondrial dysfunction is very limited.

Our Goals

We recently identified the activation of metabolic stress responses in dysfunctional neurons, which we showed to be essential in sustaining neuronal viability when mitochondrial function is compromised. These findings suggest a previously unappreciated degree of metabolic flexibility in nerve cells that provide new mechanistic insights into the processes leading to neurodegeneration.

Building on these premises, our lab is currently working on understanding the regulatory checkpoints behind this metabolic rewiring with the aim manipulate them for reverting degeneration.

Unraveling the mechanisms behind metabolic rewiring in dysfunctional neurons holds promise for developing therapeutic approaches that could potentially slow or halt the progression of neurodegenerative disorders.

Key Publications

  1. Motori E#, Giavalisco P. 13C isotope labeling and mass spectrometric isotope enrichment analysis in acute brain slices. Methods Mol Biol. 2023
  2. Motori E*, Atanassov I, Wendler S, Folz-Donahue K,  Sakthivelu V, Giavalisco P, Toni N, Puyal JP, Larsson NG*. Neuronal metabolic rewiring promotes resilience to neurodegeneration caused by mitochondrial dysfunction. Science Advances 2020 Aug 28;6(35):eaba8271.
  3. Rumyantseva A, Motori E, Trifunovic A. DARS2 is indispensable for Purkinje cell survival and protects against cerebellar ataxia. Hum Mol Genet. 2020 Oct 10;29(17):2845-2854. doi: 10.1093/hmg/ddaa176. PMID: 32766765.
  4. Gӧbel J, Engelhardt E, Pelzer P, Sakthivelu V, Jahn HM, Jevtic M, Folz-Donahue K, Kukat C, Schauss A, Frese CK, Giavalisco P, Ghanem A, Conzelmann KK, Motori E*, Bergami M*. Mitochondria-Endoplasmic Reticulum Contacts in Reactive Astrocytes Promote Vascular Remodeling. Cell Metab. 2020 Apr 7;31(4):791-808.e8.
  5. Motori E#, Puyal J, Toni N, Ghanem A, Angeloni C, Malaguti M, Cantelli-Forti G, Berninger B, Conzelmann KK, Götz M, Winklhofer KF, Hrelia S.*, Bergami M*,#. Inflammation-induced alteration of astrocyte mitochondrial dynamics requires autophagy for mitochondrial network maintenance.Cell Metab. 2013 18(6):844-59.