Michael Forte, Ph.D.

Michael Forte

Senior Scientist, Vollum Institute

Email: forte@ohsu.edu
Phone: 503-494-5454
Lab Phone: 503-494-5455
Office: Vollum 4419A

Forte Lab Page

PubMed Listing

 

Background

Michael Forte is a senior scientist at the Vollum Institute and a professor in the Departments of Molecular and Medical Genetics, Cell and Developmental Biology, and Physiology and Pharmacology in the School of Medicine. After being awarded his B.S. from the University of Notre Dame in 1973, Forte earned his Ph.D. in Genetics from the University of Washington in 1978. He then went to the University of Wisconsin for four years of postdoctoral research in Molecular Biology. In 1982, Forte became an assistant professor at Case Western Reserve University, where he remained until his appointment to the Vollum in 1986.

 

Summary of Current Research

The Forte lab is investigating the role of mitochondria in the overall regulation of cellular calcium (Ca2+). Ca2+ ions probably represent the most ubiquitous signaling pathway in all cells. Mitochondria are now recognized as initiators and transducers of a range of cell signals, participating in neuronal functions like synaptic plasticity and processes central to activation and amplification of programmed cell death. Moreover, as the main source of cellular ATP, mitochondria must respond to fluctuating energy demands of the cell. As local and global fluctuations in Ca2+ concentration are ubiquitous in eukaryotic cells and are the common factor in a wide array of intra- and inter-cellular signaling cascades, the relationships between mitochondrial function and Ca2+ transients is currently a subject of intense scrutiny. The mitochondrial Ca2+ pool oscillates rapidly in synchrony with cytosolic Ca2+ and thus, mitochondria have the ability to shape cytosolic Ca2+ transients. Mitochondria also respond to Ca2+ uptake by upregulating energy production, thus integrating metabolism with local Ca2+ signaling. The Forte lab is interested in the reciprocal effects of Ca2+ on mitochondria and mitochondria on the Ca2+ signals. Using genetic approaches in mice and Drosophila, the goal is to understand the response of mitochondria to Ca2+, the pathways by which Ca2+ accumulates into mitochondria, and the potential role of mitochondrial Ca2+ in neurodegenerative disease processes. Our studies focus on two pathways by which mitochondrial Ca2+ levels are modulated.

 

Selected Publications

Sileikyte J, Forte M. (2016) Shutting down the pore: The search for small molecule inhibitors of the mitochondrial permeability transition. Biochim. Biophys. Acta. 1857:1197-1202.

Roy S, Sileikyte J, Neuenswander B, Hedrick MP, Chung TD, Aubé J, Schoenen FJ, Forte MA, Bernardi P. (2016) N-phenylbenzamides as potent inhibitors of the mitochondrial permeability transition pore. Chem. Med. Chem. 11:283-288.

Roy S, Sileikyte J, Schiavone M, Neuenswander B, Argenton F, Aubé J, Hedrick MP, Chung TD, Forte MA, Bernardi P, Schoenen FJ. (2015) Discovery, synthesis, and optimization of diarylisoxazole-3-carboxamides as potent inhibitors of the mitochondrial permeability transition pore. Chem. Med. Chem. 10:1655-1671.

Bernardi P, Rasola A, Forte M, Lippe G. (2015) The mitochondrial permeability transition pore: Channel formation by F-ATP synthase, integration in signal transduction, and role in pathophysiology. Physiol. Rev. 95:1111-1155.

Carraro M, Giorgio V, Sileikyte J, Sartori G, Forte M, Lippe G, Zoratti M, Szabò I, Bernardi P. (2014) Channel formation by yeast F-ATP synthase and the role of dimerization in the mitochondrial permeability transition. J. Biol. Chem. 289:15980-15985.

Sileikyte J, Blachly-Dyson E, Sewell R, Carpi A, Menabò R, Di Lisa F, Ricchelli F, Bernardi P, Forte M. (2014) Regulation of the mitochondrial permeability transition pore by the outer membrane does not involve the peripheral benzodiazepine receptor (Translocator Protein of 18 kDa (TSPO)). J. Biol. Chem. 289:13769-13781.

Su K, Bourdette D, Forte M. (2013) Mitochondrial dysfunction and neurodegeneration in multiple sclerosis. Front. Physiol. 4:169.

Back to Faculty List