Mitochondria Play a Vital Role in T-Cell Proliferation and Memory Development

Recent research led by experts at Northwestern University has shed light on the crucial role mitochondria play in supporting T-cell growth and immune memory formation. Published in Nature Immunology, the study explores how mitochondrial metabolism influences immune responses, particularly in combating cancer and infections. Investigators engineered mice lacking mitochondrial complex III, a key component of the electron transport chain responsible for electron transfer and ATP production. These mice showed diminished cellular respiration, leading to impaired proliferation of CD8+ T-cells during viral infections. Notably, the absence of complex III caused these T-cells to undergo rapid exhaustion after short-term stimulation, a phenomenon traditionally associated with chronic infections.

Furthermore, the study demonstrated that mitochondrial complex III deficiency also hampers the development of T-cell memory, which is essential for long-term immunity. Interestingly, when researchers introduced the alternative oxidase (AOX) protein derived from C. intestinalis into these deficient T-cells, some metabolic functions and proliferation were restored without ROS production. However, memory formation was not rescued, indicating that ROS generation during mitochondrial activity is vital for establishing immune memory.

Dr. Navdeep Chandel explained that mitochondrial respiration supports T-cell proliferation and prevents exhaustion, highlighting mitochondria as central regulators of T-cell health. These findings offer promising avenues for designing targeted therapies to enhance immune responses by modulating mitochondrial functions, potentially improving immunotherapy strategies against cancer and infectious diseases.

Overall, this research emphasizes the importance of mitochondrial health in immune cell function, fostering new understandings of how cellular energy production influences immune resilience and memory development.

Source: https://medicalxpress.com/news/2025-07-mitochondria-cells-proliferation-memory-formation.html