Major Research Areas
Researchers in the College of Graduate Studies focus their efforts where it truly matters—on the diseases and illnesses that affect many people. Much of our research activity is grouped into four areas of concentration: cancer; infectious diseases; disorders of the nervous system; and diabetes, metabolic disorders and cardiovascular diseases.
Xin Jie Chen, PhD
- Professor of Biochemistry and Molecular Biology
Research Programs and Affiliations
- Biochemistry and Molecular Biology
- Biomedical Sciences Program
- Research Pillars
Education & Fellowships
- PhD: University of Paris-Sud, 1987, Molecular and Cellular Genetics
- Mitochondrial biogenesis and inheritance, aging and aging-related degenerative diseases.
Link to PubMed (Opens new window. Close the PubMed window to return to this page.)
Mitochondria are the powerhouses that generate energy by oxidative phosphorylation (OXPHOS) to support cellular activities, and are the integrators of cellular signals that promote different forms of cell death. Mitochondria are also known as the "powerhouses of diseases and aging", as mitochondrial dysfunction is associated with a rapidly growing number of aging-related neuromuscular degenerative diseases and metabolic disorders. How the mitochondrial function deteriorates during aging and how this in turn induces cellular degeneration are poorly understood. We use yeast, cultured cell lines and mouse as model systems to address these fundamental questions.
The ongoing research in our laboratory is focused on the following three projects:
(1) We are interested to understand how mitochondrial dysfunction contributes to aging and aging-related diseases.
(2) We are interested to identify evolutionarily conserved pathways that can potentially delay and possibly, reverse mitochondria-induced cellular degeneration.
(3) We investigate the mechanisms of mitochondrial DNA recombination, replication and repair. Elucidating these fundamental processes could help better understanding how the mitochondrial system degenerates during aging.
Chen, X.J. (2013) Mechanism of homologous recombination and implications for aging-related deletions in mitochondrial DNA. Microbiology and Molecular Biology Reviews 77:476-96
La T, Clark-Walker GD, Wang X, Wilkens S, Chen XJ. (2013) Mutations on the N-terminal edge of the DELSEED loop in either α or β subunit of the mitochondrial F1-ATPase enhance ATP hydrolysis in the absence of the central γ rotor. Eukaryote Cell 12:1451-61
Mbantenkhu, M., Wierzbicki, S., Wang, X., Guo, S., Wilkens, S., Chen, X.J. (2013) A short carboxyl-terminal tail is required for single-stranded DNA binding, higher-order structural organization, and stability of the mitochondrial single-stranded annealing protein Mgm101. Mol Biol Cell 24:1507-18.
Liu Y, Chen XJ. (2013) Adenine nucleotide translocase, mitochondrial stress, and degenerative cell death. Oxid Med Cell Longev. 2013:146860. Epub 2013 Jul 18.
Wang X, Mbantenkhu M, Wierzbicki S, Chen XJ. (2013) Preparation of the Mgm101 recombination protein by MBP-based tagging strategy. J Vis Exp. Jun 25;(76). doi: 10.3791/50448.
Nardozzi, J.D. *, Wang, X.* (* equal contribution), Mbantenkhu, M., Wilkens, S. and Chen, X.J. (2012) A properly configured ring structure is critical for the function of the mitochondrial DNA recombination protein, Mgm101. J Biol Chem 287:37259-68.
Chen, X.J. (2011) The search for nonconventional mitochondrial determinants of aging. Mol Cell 42:271-273.
Mbantenkhu, M.*, Wang, X.* (* equal contribution), Nardozzi, J.D., Wilkens, S., Hoffman, E., Patel, A., Costrove, M.S. and Chen, X.J. (2011) Mgm101 is a Rad52-related protein required for mitochondrial DNA recombination. J Biol Chem 286:42360-70.
Kucejova B, Li L, Wang X, Giannattasio S, Chen XJ. (2008) Pleiotropic effects of the yeast Sal1 and Aac2 carriers on mitochondrial function via an activity distinct from adenine nucleotide transport. Mol Genet Genomics. 280:25-39.
Wang X, Salinas K, Zuo X, Kucejova B, Chen XJ. (2008) Dominant membrane uncoupling by mutant adenine nucleotide translocase in mitochondrial diseases. Hum Mol Genet. 17:4036-44.
Wang X, Zuo X, Kucejova B, Chen XJ. Reduced cytosolic protein synthesis suppresses mitochondrial degeneration (2008) Nat Cell Biol. 10:1090-7.
OTHER SIGNIFICANT PUBLICATIONS:
Chen, X.J. (co-corresponding author), Wang, X.W. and Butow R.A. (2007) Yeast aconitase binds and provides metabolically coupled protection to mitochondrial DNA. PNAS 104:13738-13743.
Chen, X.J., Wang, X.W., Kaufman, B.A. and Butow, R.A. (2005) Aconitase couples metabolic regulation to mitochondrial DNA maintenance. Science 307:714-717.
Chen, X.J. and Butow, R.A. (2005) Organization and inheritance of mitochondrial nucleoids. Nature Review/Genetics 6:815-825.
Zuo, X.M., Clark-Walker, G.D. and Chen, X.J (2002). The mitochondrial nucleoid protein, Mgm101p, of Saccharomyces cerevisiae is involved in the maintenance of rho+ and ori/rep-devoid petite genomes but is not required for hypersuppressive rho- mtDNA. Genetics 160:1389-1400.
Chen, X.J., Guan, M.X. and Clark-Walker, G,D. (1993) MGM101, a nuclear gene involved in maintenance of the mitochondrial genome in Saccharomyces cerevisiae. Nucleic Acid Res. 21:3473-3477.
Mitochondrial carriers and diseases
Chen, X.J. (2004) Sal1p, a calcium-dependent carrier protein that suppresses an essential cellular function associated with the Aac2p isoform of ADP/ATP translocase in Saccharomyces cerevisiae. Genetics 167:607-617.
Chen, X.J. (2002) Induction of an unregulated channel by mutant nucleotide translocase suggests an explanation for human ophthalmoplegia. Human Molecular Genetics 16: 1835-1843.
Suppression of mitochondrial stress (rho-zero-lethality)
Clark-Walker, G.D. and Chen, X.J. (2001) Dual mutations reveal interactions between components of oxidative phosphorylation in Kluyveromyces lactis. Genetics 159, 929-938.
Chen, X.J. and Clark-Walker, G.D. (2000) The yeast petite mutation: fifty years on. International Review of Cytology. 194, 197-237. (invited review, featured research on the cover page).
Chen, X.J. and Clark-Walker, G.D. (1999) Alpha and beta subunits of F1-ATPase are required for survival of petite mutants in Saccharomyces cerevisiae. Mol. Gen. Genet. 262, 898-908.
Chen, X.J. and Clark-Walker, G.D. (1996) The mitochondrial genome integrity gene, MGI1, of Kluyveromyces lactis encodes the beta-subunit of F1-ATPase. Genetics 144:1445-1454.
Clark-Walker, G.D. and Chen, X.J. (1996) A vital function for mitochondrial DNA in the petite-negative yeast Kluyveromyces lactis. Mol. Gen. Genet. 252:746-750.
Chen, X.J. and Clark-Walker, G.D. (1995) Specific mutations in alpha- and gamma-subunits of F1-ATPase affect mitochondrial genome integrity in the petite-negative yeast Kluyveromyces lactis. EMBO J. 14:3277-3286.
Chen, X.J. and Clark-Walker, G.D. (1993) Mutations in MGI genes convert Kluyveromyces lactis into a petite-positive yeast. Genetics 133:517-525.