Mitochondria are very versatile organelles and they are involved in a plethora of cellular functions, such as energy production, regulation of death pathways, calcium buffering. Therefore, their dysfunction has been related to many pathological conditions, ranging from neurodegenerative disorders to cancer and metabolic diseases. Hence, their dynamic proteome is particularly important in defining their healthy state, the dynamics of the mitochondrial network and, in turn, the cellular conditions. The definition of proteins associated to mitochondria in specific physiological or pathological conditions is the main goal of several research fields and proteomics should be the approach to achieve this outcome.

The mitochondrial Italian Human Proteome Project initiative (mt-HPP) is a Human Proteome Organization (HUPO) initiative led by the Italian Proteomics Association (ItPA), focused on human mitochondrial proteins. The main goal of this effort is to obtain robust information about the integrative role of proteins acting at the mitochondrial level, considering both those encoded by the mitochondrial DNA (mt-DNA) and the nuclear encoded proteins.

Current lines of work:

• Definition of mitochondrial proteome by characterization of all mitochondrial proteins or mitochondria-associated proteins and their interaction in health and disease.
• Definition of a functional mitochondrial proteome.
• Development of standardized methods for mitochondria preparation.
• Characterization of the mitochondrial proteome/interactome in neurodegenerative diseases.
• Characterization of the mitochondrial proteome/interactome in metabolic diseases.
• Identification of three missing proteins in the mitochondrial proteome of three common cell lines.
• Definition of an updated functional mitochondrial human proteome network.

Fasano M, Alberio T, Babu M, Lundberg E, Urbani A. Towards a functional definition of the mitochondrial human proteome. EuPA Open Proteomics. 2016;10: 24-27. doi:10.1016/j.euprot.2016.01.004

Di Pierro A, Bondi H, Monti C, Pieroni L, Cilio E, Urbani A, Alberio T, Fasano M, Ronci M. Experimental setup for the identification of mitochondrial protease substrates by shotgun and top-down proteomics. EuPA Open Proteomics. 2016;11: 1-3. doi:10.1016/j.euprot.2016.02.00.

Links:

Papers:

Monti C, Lane L, Fasano M, Alberio T. Update of the Functional Mitochondrial Human Proteome Network. J Proteome Res. 2018 Oct 8. doi: 10.1021/acs.jproteome.8b00447. [Epub ahead of print] PubMed PMID: 30230342.

Costanzo M, Cevenini A, Marchese E, Imperlini E, Raia M, Del Vecchio L, Caterino M, Ruoppolo M. Label-Free Quantitative Proteomics in a Methylmalonyl-CoA Mutase-Silenced Neuroblastoma Cell Line. Int J Mol Sci. 2018 Nov 13;19(11). pii: E3580. doi: 10.3390/ijms19113580. PubMed PMID: 30428564; PubMed Central PMCID: PMC6275031.

Walter C, Gonczarowska-Jorge H, Sickmann A, Zahedi RP, Meisinger C, Schmidt O. Advanced tools for the analysis of protein phosphorylation in yeast mitochondria. Anal Biochem. 2018 Aug 1;554:23-27. doi: 10.1016/j.ab.2018.05.022. Epub 2018 May 24. PubMed PMID: 29803787.

Ronci M, Pieroni L, Greco V, Scotti L, Marini F, Corasolla Carregari V, Cunsolo V, Foti S, Aceto A, Urbani A. Sequential Fractionation Strategy Identifies Three Missing Proteins in the Mitochondrial Proteome of Commonly Used Cell Lines. J Proteome Res. 2018 Oct 5. doi: 10.1021/acs.jproteome.8b00422. [Epub ahead of print] PubMed PMID: 30284448

Tripodi F, Castoldi A, Nicastro R, Reghellin V, Lombardi L, Airoldi C, Falletta E, Maffioli E, Scarcia P, Palmieri L, Alberghina L, Agrimi G, Tedeschi G, Coccetti P. Methionine supplementation stimulates mitochondrial respiration. Biochim Biophys Acta Mol Cell Res. 2018 Dec;1865(12):1901-1913. doi: 10.1016/j.bbamcr.2018.09.007. Epub 2018 Oct 2. PubMed PMID: 30290237

Urbani A, De Canio M, Palmieri F, Sechi S, Bini L, Castagnola M, Fasano M, Modesti A, Roncada P, Timperio AM, Bonizzi L, Brunori M, Cutruzzolà F, De Pinto V, Di Ilio C, Federici G, Folli F, Foti S, Gelfi C, Lauro D, Lucacchini A, Magni F, Messana I, Pandolfi PP, Papa S, Pucci P, Sacchetta P; Italian Mt-Hpp Study Group-Italian Proteomics Association (www.itpa.it). The mitochondrial Italian Human Proteome Project initiative (mt-HPP). Mol Biosyst. 2013 Aug;9(8):1984-92. doi: 10.1039/c3mb70065h. Epub 2013 May 28.

PT, Bondi H, Colombo F, Alloggio I, Pieroni L, Urbani A, Fasano M. Mitochondrial proteomics investigation of a cellular model of impaired dopamine homeostasis, an early step in Parkinson's disease pathogenesis. Mol Biosyst. 2014 Jun;10(6):1332-44. doi: 10.1039/c3mb70611g. Epub 2014 Mar 28. PubMed PMID:24675778.

Monti C, Bondi H, Urbani A, Fasano M, Alberio T. Systems biology analysis of the proteomic alterations induced by MPP(+), a Parkinson's disease-related mitochondrial toxin. Front Cell Neurosci. 2015 Feb 2;9:14. doi:10.3389/fncel.2015.00014. eCollection 2015. PubMed PMID: 25698928

Ciregia F, Giusti L, Ronci M, Bugliani M, Piga I, Pieroni L, Rossi C, Marchetti P, Urbani A, Lucacchini A. Glucagon-like peptide 1 protects INS-1E mitochondria against palmitate-mediated beta-cell dysfunction: a proteomic study. Mol Biosyst. 2015 Jun;11(6):1696-707. doi: 10.1039/c5mb00022j. PubMed PMID: 25912719.

Links to other HPP groups:

Future meetings and activities:

Leadership:

Mauro Fasano, Chair