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Xin Jie Chen, PhD

Weiskotten Hall
766 Irving Avenue
Syracuse, NY 13210
Xin Jie Chen's email address generated as an image






Biochemistry and Molecular Biology
Biomedical Sciences Program


Mitochondrial biology, stress signaling and aging-related degenerative diseases.


PhD: University of Paris-Sud, 1987, Molecular and Cellular Genetics


University of Texas Southwestern Medical Centers, 2003-2007



Mitochondria are known as the powerhouses in the cell that generate cellular energy by oxidative phosphorylation (OXPHOS). Mitochondria are also the integrator of intracellular and environmental stress signals that modulate tissue homeostasis and promote cell death. Mitochondrial dysfunction is associated with many aging-related degenerative diseases and metabolic disorders. We investigate how mitochondrial damage induces cellular degeneration and the development of degenerative diseases during aging. We use yeast, cultured human cells and mouse as model systems to address this question.




  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 toxic 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 affects cell fitness and causes cell death, and to identify pathways that protect cells against mPOS.
  2. Implication of mPOS in muscle atrophy, cardiac function, energy homeostasis and neurodegeneration - 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 and anti-mPOS response play a role in aging-associated muscle wasting, cardiac function remodeling, body weight homeostasis and neurodegeneration.
  3. We investigate molecular pathways that are involved in the maintenance of mitochondrial DNA integrity.


For more information on my lab, go to:



Wang, X.W., Zuo, X.M., Kucejova, B. and Chen, X.J. (2008) Reduced cytosolic protein synthesis suppresses mitochondrial degeneration. Nature Cell Biology 10:1090-1097.

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.

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)

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)

Wang, X., Middleton, F.A., Tawil, R. & Chen, X.J. (2022) Cytosolic proteostatic adaptation to mitochondrial stress causes progressive muscle wasting. iScience, 25, 103715, January 21, 2022.

Mishra, G., Coyne, L. and Chen, X.J. (2023) Adenine nucleotide carrier protein dysfunction in human disease. IUBMB Life 75:911-925 (invited review).

Coyne, L.P., Wang, X., Song, J., de Jong, E., Schneider, K., Massa, P., Middleton, F., Becker, T. and Chen, X.J. (2023) Mitochondrial protein import clogging as a mechanism of disease. eLife 2023;12:e84330. DOI:

Coyne, L.P., Rana, A., Wang, X., Bhagwagar, S., Umino, Y., Solessio, E.C., Middleton, F. and Chen, X.J. Mitochondrial protein import stress augments alpha-synuclein aggregation and neurodegeneration independent of bioenergetics. BioRxiv. doi:



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