陈新杰博士

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教育

研究抽象

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.

项目

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). 因此, mitochondrial damage can directly cause proteostatic stress in the cytosol in a manner independent of bioenergetic defect. 使用基于细胞的方法, 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, 心脏功能, 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, 心功能重塑, 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: www.xinjiechenlab.com

代表的出版物:

王,X.W.左，X.M.库切约娃，B. 陈，X.J. (2008) Reduced cytosolic protein synthesis suppresses mitochondrial degeneration. Nature Cell 医学杂志ogy 10:1090-1097.

王,X. 陈，X.J. (2015) A cytosolic network suppressing mitochondria-mediated proteostatic stress and cell death. 自然524:481 - 484. (For Commentaries and highlights, see News & Views - Surviving Import Failure, Nature 524:419-420; 研究 Highlights - Death by Cytoplasmic Accumulation, Nature Chemical 医学杂志ogy 11:633; New & Noteworthy: The latest Buzz on Streassed-Out Mitochondria, SGD. http://www.yeastgenome.org/blog/the-latest-buzz-on-stressed-out-mitochondria)

刘,Y.王，X. 陈，X.J. (2015) Misfolding of mutant adenine nucleotide translocase in yeast supports a novel mechanism of Ant1-induced muscle diseases. 摩尔. 医学杂志. 细胞26:1985 - 1994.

科因左.P. 陈，X.J. (2018) mPOS - a novel trigger of cell death with implications for neurodegeneration (Special Issue: ROS and Mitochondria in Modulating Nervous System Function). 2月列托人. 592:759-775. (邀请审查)

刘Y.*，王，W.*，科因，L.P.* (*equal contributions), Yang, Y.，齐，Y.米德尔顿·F.A.，陈，X.J. (2019) Mitochondrial carrier protein overloading and misfolding induce aggresomes and proteostatic adaptations in the cytosol. 摩尔ecular 医学杂志ogy of the Cell 30:1272-1284. (Featured cover and highlighted article)

王,X.米德尔顿，F.A.，塔威尔，R. & 陈,X.J. (2022) Cytosolic proteostatic adaptation to mitochondrial stress causes progressive muscle wasting. iScience, 25, 103715, January 21, 2022.

Mishra G.科因，L. 陈，X.J. (2023) Adenine nucleotide carrier protein dysfunction in human disease. IUBMB Life 75:911-925 (邀请审查).

科因左.P.王，X.宋杰.德容，E.施耐德，K.马萨，P.米德尔顿，F.贝克尔，T. 陈，X.J. (2023) Mitochondrial protein import clogging as a mechanism of disease. eLife 2023; 12: e84330. DOI: http://doi.org/10.7554 / eLife.84330.

科因左.P.拉纳，A.王，X.巴格瓦格，S.， Umino, Y.索莱西奥，E.C.米德尔顿，F. 陈，X.J. Mitochondrial protein import stress augments alpha-synuclein aggregation and neurodegeneration independent of bioenergetics. BioRxiv. doi: http://doi.org/10.1101/2022.09.20.508793