CMMC: Bergami, Matteo

Introduction

Accruing evidence indicates that glial cells play pivotal roles in maintaining multiple forms of metabolic coupling with neurons and the brain microvasculature. In particular, astrocytic end-feet functionally ensheathe most of the vascular network and serve as specialized exchange sites for ions and energy substrates with brain parenchyma. While in physiological conditions these functions contribute to neurovascular coupling, the precise sub-cellular changes occurring at the glio-vascular interface during brain injury are much less understood.

We have recently shown an important role for mitochondrial network dynamics in perivascular astrocytic end-feet during injury, and how altering these dynamics impacts vascular remodeling. A major focus of this funding period will therefore be that of investigating specific signalling pathways linked to mitochondrial dynamics in perivascular astrocytes. The expected results will disclose the relevance of astroglial metabolism in sustaining brain tissue remodelling and how glial cell manipulation may facilitate tissue repair.

Our Aims

Assessing the role of specific mitochondrial-derived signaling pathways in reactive astrocytes
Characterization of mitochondrial metabolism in reactive astrocytes

Project Related Publications

Göbel J, Pelzer P, Engelhardt E, Sakthivelu V,Jahn HM, Jevtic M, Folz-Donahue K, Kukat C, Schauss A, Frese CK, Ghanem A, Conzelmann KK, Motori E, Bergami M. Mitochondrial fusion in reactive astrocytes coordinates local metabolic domains to promote vascular repair. BioRxiv (2019); doi:https://doi.org/10.1101/657999.
Göbel J, Motori E, Bergami M. Spatiotemporal control of mitochondrial network dynamics in astroglial cells. Biochem Biophys Res Commun(2018); 500:17-25.
Motori, E.^#, Puyal, J., Toni, N., Ghanem, A., Angeloni, C., Malaguti, M., Cantelli-Forti, G., Berninger, B., Conzelmann, K.K., Götz, M., Winklhofer, K., Hrelia, S.*, and Bergami, M.*^,#Inflammation-induced alteration of astrocyte mitochondrial dynamics requires autophagy for mitochondrial network maintenance. Cell Metab (2013); 18, 844-859. ^#co-corresponding; *equal contribution.

Publications 2020

Bergami M, and Motori E (2020). Reweaving the Fabric of Mitochondrial Contact Sites in Astrocytes. Front Cell Dev Biol 8, 592651.
Gbel 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, and Bergami M (2020). Mitochondria-Endoplasmic Reticulum Contacts in Reactive Astrocytes Promote Vascular Remodeling. Cell Metab 31, 791-808 e8.
Ricke KM, Pass T, Kimoloi S, Fahrmann K, Jungst C, Schauss A, Baris OR, Aradjanski M, Trifunovic A, Eriksson Faelker TM, Bergami M, and Wiesner RJ (2020). Mitochondrial Dysfunction Combined with High Calcium Load Leads to Impaired Antioxidant Defense Underlying the Selective Loss of Nigral Dopaminergic Neurons. J Neurosci 40, 1975-86.