Eric A Schon
Eric A Schon
Professor of 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 unique among the constituents of the eukaryotic cell in that they 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. In addition, organellar division and mtDNA replication are stochastic processes unrelated to the cell cycle, and mtDNA gene organization, DNA replication, RNA transcription, and protein translation all have a prokaryotic "look" about them. This latter feature is no surprise, given that mitochondria were once bacteria that were taken up by the proto-eukaryotic cell early in evolution. Biochemically, the most relevant aspect of mitochondrial function is the production of oxidative energy via the respiratory chain and oxidative phosphorylation.

Mitochondrial diseases have turned out to be equally unusual. There are maternally-inherited, mendelian-inherited, sporadic, and even environmentally induced mitochondrial disorders, most of which are either severely debilitating or fatal. We are studying the molecular basis of a number of these diseases, most of which are heteroplasmic (i.e. both mutant and wild-type mtDNAs coexist in varying proportions in the same patient), using a novel tissue culture system called "rho cells." These cells contain mitochondria, but the mitochondria are completely devoid of mtDNAs, and are thus respiratorily deficient. We have transferred heteroplasmic mitochondria from patients to these rho cells, thereby creating 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 are using cybrid technology not only to study genotype phenotype relationships, but also to ask basic questions about mitochondrial biogenesis (e.g. mitochondrial fusion and exchange of genetic information).

We have begun a project on mitochondrial gene therapy, in order to ameliorate the effects of a known pathogenic (and fatal) mtDNA mutation that affects ATP synthesis. In addition, we are trying to make the first "transmitochondrial" mouse model of a human mtDNA disease.
(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. Lim YM, de Groof AJC, Bhattacharjee MK, Figurski DH, Schon EA: (2008) Bacterial conjugation in the cytoplasm of mouse cells.  Infect. Immun.  76: 5110-5119

5. 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

6. Yang H, Brosel B, Acin-Perez R, Nishino I, Khan R, Goldberg IJ, Manfredi G, Schon EA: (2010) Analysis of mouse models of cytochrome c oxidase deficiency owing to mutations in Sco2.  Human Molec. Genet.  19: 170-180

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