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 (UPRmt), 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.