Marisa Brini

The Brini Lab research activity is mainly focused on calcium signaling, mitochondria biology and their crosstalk in cell physiology and pathophysiology. Our research aims to investigate the effects of mitochondrial dysfunction and Ca²⁺ signalling dysregulation associated with neurodegenerative diseases, i.e., in the pathogenesis of Parkinson’s disease (PD). The role of proteins whose mutations are linked with familial PD (i.e., alpha-synuclein, PINK1, Parkin and DJ-1) in mitochondrial processes (i.e., mitochondrial calcium signaling, bioenergetics, mitophagy etc.) and in the crosstalk between mitochondria and endoplasmic reticulum are currently investigated using different cellular models by biochemical, molecular, and cellular biology approaches and by live cell imaging and confocal microscopy.

More recently we expanded our research interest to deeply explore mitochondria communication with other organelles, i.e., lysosomes, nucleus, peroxisomes, and plasma membrane, etc. since it is now widely recognized that organelles proximity represents a critical hub for the transfer of information and its molecular understanding is a challenge to identify new targets for therapeutical intervention.

Currently ongoing projects focus on

- the analysis of Ca²⁺ homeostasis in living cells carrying mutations in isoform 2 and 3 of the plasma membrane Ca²⁺-ATPase causing cerebellar ataxia

- the study of mitochondria and Ca²⁺ handling with a special attention to the action of Parkinson disease- related proteins (alpha-synuclein, PINK1, Parkin and DJ-1) on mitochondrial function

- the study of the relationship between mitochondria and the other organelles, of their communication by the development and application of new recombinant tools based on splitGFP to monitor organelles contact sites and sub-mitochondrial distribution of proteins of interest.

Rizzuto, R., Simpson, A.W.M., Brini, M. & Pozzan, T.: Rapid changes of mitochondrial Ca²⁺ revealed by specifically targeted recombinant aequorin. Nature (1992) 358, 325-328.

Rizzuto, R., Brini, M., Murgia, M. & Pozzan, T. : Microdomains of high Ca²⁺ close to inositol-triphosphate sensitive channels are sensed by neighboring mitochondria. Science (1993), 262, 744-747.

Brini, M., Pinton, P., King, M.P., Davidson, M., Schon, E. A. & Rizzuto, R.: A calcium signalling defect in the pathogenesis of a mtDNA-inherited oxidative phosphorylation deficiency. Nature Med. (1999), 5, 951-954.

Calì,T., Ottolini, D., Negro, A., Brini,M. Alpha-synuclein controls mitochondrial calcium homeostasis by enhancing endoplasmic reticulum-mitochondria interactions. J Biol. Chem. (2012), 287, 17914-17929.

Zanni G, Calì T, Kalscheuer VM, Ottolini D, Barresi S, Lebrun N, Montecchi-Palazzi L, Hu H, Chelly J, Bertini E, Brini M, Carafoli E. A Mutation of Plasma Membrane Ca²⁺ ATPase Isoform 3 in a Family with X-Linked Congenital Cerebellar Ataxia impairs Ca²⁺ Homeostasis. Proc Natl Acad Sci U S A. (2012), 109, 14514-14519

Calì, T., Ottolini, D., Negro,A, Brini, M. Enhanced parkin levels favour ER-mitochondria crosstalk and guarantee Ca²⁺ transfer to sustain cell bioenergetics. Biochim Biophys Acta. Molecular Basis of Disease (2013), 1832, 495-508.

Ottolini, D., Calì, T.,Negro A., Brini, M. The Parkinson disease-related protein DJ-1 counteracts mitochondrial impairment induced by the tumour suppressor protein p53 by enhancing Endoplasmic Reticulum-mitochondria tethering. Hum Mol Gen (2013), 22, 2152-2168.

Cieri, D.,Vicario, M.Giacomello,M. Vallese,F.,Filadi,R.,Wagner,T. Pozzan,T. Pizzo,P. Scorrano, L., Brini, M. Calì, T. SPLICS: a split green fluorescent protein-based contact site sensor for narrow and wide heterotypic organelle juxtaposition. Cell Death Differ. (2018) 25(6):1131-1145.

Vallese F, Catoni C, Cieri D, Barazzuol L, Ramirez O, Calore V, Bonora M, Giamogante F, Pinton P, Brini M, Calì T. An expanded palette of improved SPLICS reporters detects multiple organelle contacts in vitro and in vivo. Nat Commun. 2020 Nov 27;11(1):6069. doi: 10.1038/s41467-020-19892-6.

Calì T, Brini M. Quantification of organelle contact sites by split-GFP-based contact site sensors (SPLICS) in living cells. Nat Protoc. 2021 Nov;16(11):5287-5308. doi: 10.1038/s41596-021-00614-