Eric A Schon
Eric A Schon
Lewis P. Rowland Professor of Neurology (in Genetics and Development)

Address: 630 West 168th Street P&S 4-449 New York NY 10032
Phone: 212-305-1665
Fax: 212-305-3986


Education and Training:
Ph.D. 1982, University of Cincinnati
Postdoctoral Fellow 1982, Harvard University
Associate Research Scientist 1984, Columbia University
bullet  Department of Genetics and Development
bullet  Department of Neurology
Training Activities:
bullet  Department of Genetics & Development
bullet  MD/PhD Program
bullet  Integrated Program in Cellular, Molecular and Biophysical Studies
Research Summary:
(800 words, max)
Mitochondrial genetics and the molecular basis of human mitochondrial disease.

Current Research:
Mitochondria are semi-autonomous organelles that contain their own genetic machinery. As such, they operate under the dual genetic controls of nuclear DNA (nDNA) and mitochondrial DNA (mtDNA).

Mitochondrial genetics differs markedly from mendelian genetics, because first, mitochondria are inherited exclusively from the mother, and second, there are hundreds or thousands of mitochondria (and mtDNAs) per cell. Biochemically, the most relevant aspect of mitochondrial function is the production of oxidative energy via the respiratory chain and oxidative phosphorylation.

There are maternally-inherited, mendelian-inherited, sporadic, and even environmentally-induced mitochondrial disorders, most of which are fatal. We are studying the molecular basis of a number of these diseases, often using cytoplasmic hybrids, or "cybrids," that contain known proportions of mutant or wild-type mtDNAs in clonal cell lines that have no contaminating mtDNA background. We have also begun a project on treating mtDNA-based disease using pharmacoligical approaches aimed at "shifting heteroplasmy" in order to restore respiratory function in patient-derived cells.

Most recently we have become interested in the pathogenesis of Alzheimer disease, and have discovered that presenilin-1, presenilin-2, and gamma-secretase activity itself, are located predominantly in a specialized subcompartment of the ER that is physically and biochemically connected to mitochondria, called mitochondria-associated ER membranes (MAM). We have found that cells from AD patients have massively increased ER-mitochondrial communication, which may help explain many of the seemingly unrelated features of the disease. We believe that this hyperconnectivity plays a fundamental role in the pathogenesis of AD, with implications for both diagnosis and treatment of this devastating disorder.
(6 max)
1. Williams JC, Sue C, Banting GS, Yang H, Glerum DM, Hendrickson WA, Schon EA: (2005) Crystal structure of human SCO1: implications for redox signaling by a mitochondrial cytochrome c oxidase "assembly" protein.  J. Biol. Chem.   280: 15202-15211

2. Santra S, Gilkerson RW, Davidson M, Schon EA: (2004) Ketogenic treatment reduces deleted mitochondrial DNAs in cultured human cells.  Ann Neurol  56: 662-669

3. Gilkerson RW, Schon EA, Hernandez E, Davidson MM: (2008) Mitochondrial nucleoids maintain genetic autonomy but allow for functional complementation.  J. Cell Biol.  181: 1117-1128

4. Area-Gomez E, de Groof AJC, Boldogh I, Bird TD, Gibson GE, Koehler CM, Yu WH, Duff KE, Yaffe MP, Pon LA, Schon EA: (2009) Presenilins are enriched in endoplasmic reticulum membranes associated with mitochondria.  Am. J. Pathol.  175: 1810-1816

5. Area-Gomez E, Lara Castillo MdC, Tambini MD, de Groof AJC, Madra M, Ikenouchi J, Umeda M, Bird TD, Sturley SL, Schon EA: (2012) Upregulated function of mitochondria-associated ER membranes in Alzheimer disease.  EMBO J.  31: 4106-4123

6. Guardia-Laguarta C, Area-Gomez E, Rüb C, Liu Y, Magrané J, Becker D, Voos W, Schon EA, Przedborski S: (2014) α-Synuclein is localized to mitochondria-associated ER membranes.  J. Neurosci.  34: 249-259

URL for lab page: