Graduate Studies Faculty
Xin Jie Chen, PhD
- Professor of Biochemistry and Molecular Biology
Research Programs and Affiliations
- Biochemistry and Molecular Biology
- Biomedical Sciences Program
Education & Fellowships
- PhD: University of Paris-Sud, 1987, Molecular and Cellular Genetics
- University of Texas Southwestern Medical Centers, 2003–2007
Mitochondrial biology, stress signaling 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. Mitochondria are also the integrators of stress signals that promote cell death. Mitochondrial dysfunction is associated with many aging-related neuromuscular degenerative diseases and metabolic disorders. We investigate how mitochondrial function deteriorates during aging and how mitochondrial damage induces cellular degeneration and neuromuscular degenerative diseases. We use yeast, cultured human cells and mouse as model systems to address these questions.
(1)Mitochondrial Precursor Over-accumulation Stress (mPOS) - We discovered that mitochondrial protein import is readily saturable within the cell and that the cytosol has a limited capacity in degrading unimported proteins. Various mitochondrial stressors, with or without directly targeting the core protein import machinery, can cause the over-accumulation of unimported proteins in the cytosol. This leads to a cytosolic stress that we named mitochondrial Precursor Over-accumulation Stress (mPOS). Thus, mitochondrial damage can directly cause proteostatic stress in the cytosol in a manner independent of bioenergetic defect. Using cell-based approaches, we are interested to learn the mechanism(s) by which mPOS causes cell death, and to identify pathways that protect cells against mPOS.
(2)mPOS and neuromuscular diseases - Mitochondrial abnormalities and cytosolic protein misfolding are probably the two most important hallmarks of aging and aging-associated degenerative diseases. The mPOS hypothesis provides a conceptual framework for reconciling these two seemingly unrelated pathways of cell degeneration. We are interested to learn whether mPOS plays a role in aging-associated muscle wasting, cardiac dysfunction and neurodegeneration, and to develop anti-mPOS interventions for the treatment of these diseases.
(3)We investigate the mechanism of mitochondrial DNA recombination, replication and repair in healthy cells and mtDNA instability in human diseases.
For more information on my lab, go to: www.xinjiechenlab.com
Wang, X. and Chen, X.J. (2015) A cytosolic network suppressing mitochondria-mediated proteostatic stress and cell death. Nature 524:481-484. (For Commentaries and highlights, see News & Views - Surviving Import Failure, Nature 524:419-420; Research Highlights - Death by Cytoplasmic Accumulation, Nature Chemical Biology 11:633; New & Noteworthy: The latest Buzz on Streassed-Out Mitochondria, SGD. https://www.yeastgenome.org/blog/the-latest-buzz-on-stressed-out-mitochondria)
Liu, Y., Wang, X. and Chen, X.J. (2015) Misfolding of mutant adenine nucleotide translocase in yeast supports a novel mechanism of Ant1-induced muscle diseases. Mol. Biol. Cell 26:1985-1994.
Coyne, L.P. and Chen, X.J. (2018) mPOS - a novel trigger of cell death with implications for neurodegeneration (Special Issue: ROS and Mitochondria in Modulating Nervous System Function). FEBS Lett. 592:759-775. (Invited review)
Guaragnella, N., L.P. Coyne, X.J. Chen* and S. Giannattasio* (2018) Mitochondria-cytosol-nucleus crosstalk: learning from Saccharomyces cerevisiae. FEMS Yeast Research 18:1-15. (Invited review).
Chen, X.J. and Clark-Walker (2018) Unveiling the mystery of mitochondrial DNA replication in yeasts. Mitochondrion 38:17-22. (Review)
Coyne, L. and X.J. Chen (2019) Consequences of inner mitochondrial membrane protein misfolding. Mitochondrion 49:46-55 (Invited review)
Liu Y.*, Wang, W.*, Coyne, L.P.* (*equal contributions), Yang, Y., Qi, Y., Middleton F.A., and Chen, X.J. (2019) Mitochondrial carrier protein overloading and misfolding induce aggresomes and proteostatic adaptations in the cytosol. Molecular Biology of the Cell 30:1272-1284. (Featured cover and highlighted article)