Ye Tian

Mitochondria are not only central organelles for cellular energy metabolism, but also key signaling hubs that sense environmental changes, regulate cell fate, and maintain tissue homeostasis. Upon mitochondrial dysfunction, cells activate adaptive programs such as the mitochondrial unfolded protein response (UPR^mt), integrated stress responses, metabolic remodeling, and organelle quality control to restore cellular homeostasis and enhance stress resistance. The intensity, duration, and developmental timing of mitochondrial stress determine whether it promotes repair and healthy longevity or contributes to tissue dysfunction and disease.

Our laboratory focuses on mitochondrial stress signaling, cellular and tissue stress resistance, and the mechanisms of aging regulation. By integrating studies in Caenorhabditis elegans, mammalian cells, and mouse models, we investigate how mitochondrial damage is sensed, communicated, and memorized across organelles, cells, tissues, and whole organisms, and how these processes influence tissue homeostasis, organismal aging, and age-related diseases.

Mitochondrial damage generates diverse retrograde signals that regulate nuclear gene expression, chromatin states, lipid metabolism, calcium signaling, and the structure and function of other organelles. We study how cells recognize distinct forms of mitochondrial stress and coordinate mitochondrial repair, organelle crosstalk, nuclear envelope integrity, and cell survival, with the goal of defining the molecular boundaries between adaptive stress responses and pathological damage.

Mitochondrial stress is not confined to the damaged cell. The nervous system can sense local changes in mitochondrial function and transmit stress-related information to the intestine, metabolic tissues, and the immune system via neurotransmitters, neuropeptides, growth factors, and other secreted signals. These pathways regulate systemic mitochondrial homeostasis, metabolism, barrier function, and lifespan. We focus on how neuronal mitochondrial stress reshapes neural activity and cell-cell communication, and explore the conservation of these inter-tissue regulatory mechanisms in aging and age-related functional decline.

Mild mitochondrial stress experienced early in life can have long-lasting effects on adulthood and even the entire lifespan, suggesting that transient organelle stress can establish durable molecular memory. We investigate how mitochondrial stress regulates chromatin remodeling, transcription factor activity, and epigenetic states, and how these changes influence subsequent stress responses, tissue function, and longevity. Our goal is to understand how developmental environment and organelle state shape individual aging trajectories.

Gut microbes and their metabolites influence host nutrient metabolism, redox balance, immune responses, and barrier function. However, the same microbe may exert markedly different effects in hosts with distinct genetic backgrounds. Using natural bacterial resources and host genetic approaches in C. elegans, we study how microbial metabolites, lipids, and cellular components regulate host mitochondrial function, stress defense, and lifespan. We further investigate how host genetic variation determines the beneficial or detrimental outcomes of microbial interventions, providing mechanistic insights for precision health strategies.

1. Zhang Q^#, Dong HY^#, Jiang YY^#, Wang ZH, Li JS, Tian Y* (2026). FUBL-3/FUBP1 Mediates Mitochondrial Stress-induced Chromatin Remodeling and Longevity. Science Advances, 12(26):eaec8143.

2. Hao XS, Yuan RW, Guo YF, Chen GY, Guo YQ, Liu LM, Lu F, Bai Y, Tian Y* (2026). Host Oxidative Response Capacity Determines Longevity Outcomes of Microbial Interventions. Aging Cell, 25(2):e70418.

3. Chen P^#, Zhang LY^#, Wu XY, Liang ZQ, Hao XS, Zhu QY, Liu Y, Zheng JR, Zhang Q, Yang QM, Zhou F, Zhou CB, Tian Y* (2026). Mitochondrial Superoxide Regulates Nuclear Envelope Integrity and Aging via Redox-mediated Lipid Metabolism. Nature Metabolism, 8(2):371-388.

4. Chen GY^#, Dong HY^#, Tian Y* (2026). Mito-nuclear Communication: From Cellular Responses to Organismal Health. Molecular Cell, 86(3):522-532.

5. Thaiss CA*, Tian Y*, Winer DA*, Linterman M*, Liston A*, Amor C*, Lowe SW*, Liu GH* (2025). Aging and Immunity. Immunity, 58(11):2609-2612.

6. Zhu HD, Zhang Q, Tian Y* and Cohen E* (2025). TGF-β Signaling as an Organismal Proteostasis Regulator. Trends in Cell Biology, 35(12):1016-1027.

7. Zhou J^#, Zhu D^#, Wang YB, Wang ZL, Zhang N, Huang XH, Zhang YQ, Wang YC, Wu XY* and Tian Y* (2025). Mitochondrial Stress Orchestrates Chromatin Remodeling and Longevity via Phosphoregulation of the NuRD Component LIN-40. SCIENCE CHINA Life Sciences, 68(11):3340-3352.

8. 张宁, 田烨* (2025). 基于荧光蛋白的生物探针设计策略及其应用[J]. 遗传, 47(7):711-728.

9. 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.

10. Liu LM^#*, Hao XS^#, Bai Y* and Tian Y* (2025). The soil Mycobacterium sp. Promotes Health and Longevity through Different Bacteria-derived Molecules in Caenorhabditis elegans. Aging Cell, 24(3):e14416.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

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

18. 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.

19. Cai YS^#, Song W^#, Li JM^#, Jing Y^#, Liang CQ^#, Zhang LY^#, Zhang X^#, Zhang WH^#, Liu BB^#, An YP^#, Li JY^#, Tang BX^#, Pei 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.

20. 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 Extension in C. elegans. Cell Reports, 39(10):110931.

21. 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.

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

23. 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.

24. 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.

25. 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.

26. 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.

27. 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.

28. 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.

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

30. 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.

31. 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.

32. 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.

33. 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