Abstract 3773: Mitochondrial fusion is required to support higher rates of respiration in proliferating cancer cells

Abstract

Proliferating cancer cells exhibit an elevated rate of glucose consumption and lactate excretion, a phenomenon described as the “Warburg effect”. Although increased glycolytic flux in proliferating cells is well established, metabolic changes associated with mitochondria still remain elusive. Here, using various inducible quiescence models and mass spectrometry-based metabolomics, we directly compared mitochondrial respiration and TCA cycle activity from the same cells in the proliferative and quiescent states. We found that mitochondrial respiration and TCA cycle flux is significantly increased during proliferation in both transformed and non-transformed cell lines. This increase was supported by mitochondrial fusion rather than mitochondrial biogenesis. Notably, as cells transitioned from a quiescent state to a proliferative state, the elongation of mitochondria occurred as quickly as 3 hours. Our results reveal that the Warburg effect, which was originally associated with dysfunctional mitochondria, does not necessitate decreased mitochondrial respiration. Rather, in many proliferating cancer cells, mitochondrial respiration is actually elevated, underscoring the importance of mitochondrial respiration during proliferation. Citation Format: Yahui Wang, Conghui Yao, Ethan Stancliffe, Ronald Fowle-Grider, Rencheng Wang, Cheng Wang, Michaela Schwaiger-Haber, Leah P. Shriver, Jason Weber, Gary J. Patti. Mitochondrial fusion is required to support higher rates of respiration in proliferating cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3773.