Abstract SY27-01: Mitochondria function in normal and cancer cells

Abstract Mitochondrial respiratory chain (RC) activity plays a crucial role in the proliferation of various cell types in vivo within the tumor microenvironment, especially in cancer cells, CD4+ and CD8+ T cells, and endothelial cells. This activity is vital for the production of ATP, which is essential for energy metabolism, and for the biosynthesis of key macromolecules. The mitochondrial respiratory chain is integral to the oxidative tricarboxylic acid (TCA) cycle, which generates intermediates that are used in anabolic pathways to synthesize lipids, proteins, and nucleotides—critical components for cell growth and division. However, the role of mitochondrial respiration is more complex in certain proliferating cells within tumor microenvironment, such as regulatory T cells (Tregs) and stem cells. In these cells, mitochondria are not as critical for the general process of cell proliferation but instead play a pivotal role in determining cell fate and function. Mitochondria influence these processes through various signaling mechanisms that affect how these cells differentiate and carry out their specialized functions. I will discuss how the mitochondrial respiratory chain functions as an anabolic engine that drives the proliferation of cancer cells, CD4+ and CD8+ T cells, and endothelial cells. I will also discuss how mitochondria act as central hubs that integrate metabolic signals to regulate the fate and function of Tregs and stem cells in vivo, highlighting the distinct yet interconnected roles mitochondria play in different cell types. Citation Format: Navdeep S. Chandel. Mitochondria function in normal and cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr SY27-01.