Ye Tian

 

 

The Tian laboratory is interested in understanding how mitochondrial surveillance mechanisms regulate the aging process. We use C. elegans as a model system, as it has a rapid lifecycle and well-studied genetics. We also explore the physiological consequence of the mitochondrial surveillance signaling pathway in mammalian systems.   

 

Aging is not merely a biological process toward the end of life. Metabolic stress in early life appears to restructure chromatin, leaving a durable epigenetic change that may influence the aging process. We found that mitochondrial stress during early life induces mitochondrial stress response (UPR^mt) and longevity via specific epigenetic regulations in C. elegans (Cell, 2016). We further revealed that early life mitochondrial perturbations alter the nuclear epigenome to induce longevity via the histone deacetylation complex NuRD in response to cellular acetyl-CoA levels (Science Advances, 2020).

 

Neuronal mitochondrial stresses communicate stress signals to peripheral tissues, coordinating organismal-wide metabolic homeostasis for optimal fitness. We found that a secreted Wnt ligand, EGL-20, coordinates mitochondrial stress signaling between neurons and the intestine (Cell, 2018). Furthermore, we found that neuronal mitochondrial stress also communicates to the germ cells, which promotes maternal inheritance of elevated levels of mtDNA via the Wnt signaling, thereby passing down a “stress memory” to offspring. The “stress memory” enables descendants with a greater tolerance to environmental stress and makes the offspring live longer with tradeoffs of delayed development and decreased fecundity (Nature Cell Biology, 2021).

 

All organisms live in a close relationship with their microbiome. The nematode C. elegans represents a great model to study how Microbiota-host interactions shape the aging process.

1. Li JS, Cui JM, Li XY, Zhu D, Chen ZH, Huang XH, Wang YC, Wu QF and Tian Y*(2025). TMBIM-2 Orchestrates Systemic Mitochondrial Stress Response via Facilitating Ca²⁺ Oscillations. Journal of Cell Biology, 224(5):e202408050.

 

2. Liu LM^#*, Hao XS^#, Bai Y* and Tian Y*(2024). The soil Mycobacterium sp. Promotes Health and Longevity through Different Bacteria-derived Molecules in Caenorhabditis elegans. Aging Cell, 24(3):e14416.

 

3. Wu JC^#, Liu Y^#, Ou LQ^#, Gan TT^#, Zhangding ZR, Yuan SP, Liu XY, Liu MZ, Li JS, Yin JH, Xin CC, Tian Y and Hu JZ* (2024). Transfer of Mitochondrial DNA into the Nuclear Genome during Induced DNA Breaks. Nature Communications, 15(1):9438.

 

4. Wang ZH^#, Zhang Q^#, Jiang YY, Zhou J and Tian Y* (2024). ASI-RIM Neuronal Axis Regulates Systemic Mitochondrial Stress Response via TGF-β Signaling Cascade. Nature Communications, 15(1):8997.

 

5. Chen P, Zhang LY, Chen D* and Tian Y* (2024). Mitochondrial Stress and Aging: Lessons from C. elegans. Seminars in Cell and Developmental Biology, 154(Pt A):69-76.

 

6. Ren J, Song MS, Zhang WQ, Cai JP, Cao F, Cao ZW, Chan P, Chen C, Chen GB, Chen HZ, Chen J, Chen XC, Ci WM, Ding BS, Ding QR, Gao F, Gao SR, Han JJ, He QY, Huang K, Ju ZY, Kong QP, Li J, Li J, Li JY, Li X, Liu BH, Liu F, Liu JP, Liu L, Liu Q, Liu Q, Liu X, Liu Y, Luo XH, Ma S, Ma XR, Mao ZY, Nie J, Peng YJ, Qu J, Ren RB, Song WH, Songyang Z, Sun L, Sun YE, Sun Y, Tian M, Tian XL, Tian Y, Wang JW, Wang SS, Wang S, Wang WG, Wang X, Wang XN, Wang YJ, Wang YF, Wong CCL, Xiang AP, Xiao YC, Xiao ZX, Xie ZW, Xiong W, Xu DC, Yang Z, Ye J, Yu W, Yue R, Zhang CT, Zhang HB, Zhang L, Zhang XC, Zhang Y, Zhang YW, Zhang ZH, Zhao TB, Zhao YZ, Zhou ZJ, Zhu DH, Zou WG, Pei G and Liu GH (2023). The Aging Biomarker Consortium Represents a New Era for Aging Research in China. Nature Medicine, 29(9):2162-2165.

 

7. 张茜^#, 王子豪^#, 田烨* (2023). 跨组织线粒体应激信号交流调控机体衰老的研究进展[J]. 遗传, 45(3):187-197.

 

8. Zhang HL^#, Li XY^#, Fan WD, Pandovski S, Tian Y* and Dillin A* (2023). Inter-tissue Communication of Mitochondrial Stress and Metabolic Health. Life Metabolism, 2(1):1-11.

 

9. Li JS^#, Cui JM^# and Tian Y* (2022). Neuron-Periphery Mitochondrial Stress Communication in Aging and Diseases. Life Medicine, 1(2):168-178.

 

10. Liu YL^#, Zhou J^#, Zhang N, Wu XY, Zhang Q, Zhang WF, Li XY and Tian Y* (2022). Two Sensory Neurons Coordinate the Systemic Mitochondrial Stress Response via GPCR Signaling in C. elegans. Developmental Cell, 57(21):2469-2482.e5.

 

11. Cai YS^#, Song W^#, Li JM^#, Jing Y^#, Liang CQ^#, Zhang LY^#, Zhang X^#, Zhang WH^#, Liu BB^#, An YP^#, Li JY^#, Tang BX^#, SY^#, Wu XY^#, Liu YX^#, Zhuang CL^#, Ying YL^#, Dou XF^#, Chen Y^#, Xiao FH^#, Li DF^#, Yang RC^#, Zhao Y^#, Wang Y^#, Wang LH^#, Li YJ^#, Ma S*, Wang S*, Song XY*, Ren J*, Zhang L*, Wang J*, Zhang WQ*, Xie ZW*, Qu J*, Wang JW*, Xiao YC*, Tian Y*, Wang GL*, Hu P*, Ye J*, Sun Y*, Mao ZY*, Kong QP*, Liu Q*, Zou QG*, Tian XL*, Xiao ZX*, Liu Y*, Liu JP*, Song MS*, Han JD* and Liu GH* (2022). The Landscape of Aging. Science China-Life Sciences, 65(12):2354-2454.

 

12. Li XY, Li JS, Zhu D, Zhang N, Hao XS, Zhang WF, Zhang Q, Liu YL, Wu XY and Tian Y* (2022). Protein Disulfide Isomerase PDI-6 Assists Wnt Secretion to Coordinate Inter-tissue UPR^mt and Lifespan. Cell Reports, 39(10):110931.

 

13. Zhu D^#, Li XY^# and Tian Y* (2022). Mitochondrial-to-nuclear Communication in Aging: An Epigenetic Perspective. Trends in Biochemical Sciences, 47(8):645-659.

 

14. Zhang Q and Tian Y* (2022). Molecular Insights into the Transgenerational Inheritance of Stress Memory. Journal of Genetics and Genomics, 49(2):89-95.

 

15. Zhang Q, Wang ZH, Zhang WF, Wen QB, Li XY, Zhou J, Wu XY, Guo YQ, Liu YL, Wei CS, Qian WF and Tian Y* (2021). The Memory of Neuronal Mitochondrial Stress is Inherited Transgenerationally via Elevated mtDNA Levels. Nature Cell Biology, 23(8):870-880.

 

16. Wang YL^#, He KX^#, Sheng BF^#, Lei XQ, Tao WY, Zhu XL, Wei Z, Fu RJ, Wang AL, Bai SD, Zhang Z, Hong N, Ye C, Tian Y, Wang J, Li MS, Zhang KG, Li L, Yang H*, Li HB*, Flavell RA* and Zhu S* (2021). The RNA Helicase Dhx15 Mediates Wnt-Induced Antimicrobial Protein Expression in Paneth Cells. PNAS, 118(4):e2017432118.

 

17. Rong BW^#, Zhang Q^#, Wan JK, Xing SH, Dai RF, Li Y, Cai JB, Xie JY, Song Y, Chen JW, Zhang L, Yan GQ, Zhang W, Gao H, Han JD, Qu QH, Ma HH*, Tian Y* and Lan F* (2020). Ribosome 18S m⁶A Methyltransferase METTL5 Promotes Translation Initiation and Breast Cancer Cell Growth. Cell Reports, 33(12):108544.

 

18. Zhu D^#, Wu XY^#, Zhou J, Li XY, Huang XH, Li JS, Wu JB, Bian Q, Wang YC and Tian Y* (2020). NuRD Mediates Mitochondrial Stress-Induced Longevity via Chromatin Remodeling in Response to Acetyl-CoA Level. Science Advances, 6(31):eabb2529.

 

19. Zhang Q^#, Wu XY^#, Chen P^#, Liu LM, Xin N, Tian Y* and Dillin A* (2018). The Mitochondrial Unfolded Protein Response is Mediated Cell-non-Autonomously by Retromer-Dependent Wnt Signaling. Cell, 174(4):870-883.e17.

 

20. Tian Y, Garcia G, Bian Q, Steffen KK, Joe L, Wolff S, Meyer BJ and Dillin A* (2016). Mitochondrial Stress Induces Chromatin Reorganization to Promote Longevity and UPR^mt. Cell, 165(5):1197-1208.

 

21. Tian Y^#, Merkwirth C^# and Dillin A* (2016). Mitochondrial UPR: A Double-Edged Sword. Trends in Cell Biology, 26(8):563-565.

 

22. Berendzen KM^#, Durieux J^#, Shao LW, Tian Y, Kim H, Wolff S, Liu Y and Dillin A* (2016). Neuroendocrine Coordination of Mitochondrial Stress Signaling and Proteostasis. Cell, 166(6):1553-1563.e10.

 

23. Russell RC, Tian Y, Yuan H, Park HW, Chang YY, Kim J, Kim H, Neufeld TP, Dillin A and Guan KL* (2013). ULK1 Induces Autophagy by Phosphorylating Beclin-1 and Activating VPS34 Lipid Kinase. Nature Cell Biology, 15(7):741-750.

 

24. Tian Y^#, Li Z^#, Hu W^#, Ren H^#, Tian E, Zhao Y, Lu Q, Huang X, Yang P, Li X, Wang X, Kovacs A, Yu L* and Zhang H* (2010a). C. elegans Screen Identifies Autophagy Genes Specific to Multicellular Organisms. Cell, 141(6):1042-1055.

 

25. Tian Y, Ren HY, Zhao Y, Lu Q, Huang XX, Yang PG and Zhang H* (2010b). Four Metazoan Autophagy Genes Regulate Cargo Recognition, Autophagosome Formation and Autolysosomal Degradation. Autophagy, 6(7):984-985.