Abstract 1573: Inhibition of acetyl-CoA carboxylase induced spindle abnormalities

Abstract Acetyl-CoA carboxylase (ACC), the rate-limiting enzyme in the de novo fatty acid synthesis pathway, is required for successful cell division in yeast, indicating that fatty acid synthesis may be regulated in order to properly safeguard nuclear and cell division. ACC is also phosphorylated during mitosis and this inhibitory phospho-ACC is accumulated at the spindle pole at metaphases. In this study, we set out to understand the role of ACC in the regulation of mitotic spindle assembly in human cells. We found that inhibition of ACC with TOFA induced spindle defects and cell death. The spindle defects induced by TOFA could be rescued by exogenous palmitic acid (PA), the immediate products of fatty acid synthesis. Inhibiting protein palmitoylating or depalmitoylating enzymes could induced spindle defects. These data indicate that well-regulated cellular PA levels and protein palmitoylation are required to assure accurate spindle assembly. In addition, the spindle microtubules comprised of α-tubulins mutated at the reported palmitoylation site exhibited disrupted dynamic instability. These results reveal that ACC may modulate tubulin palmitoylation during mitosis to delicately control MT dynamic instability and spindle assembly, thereby safeguarding nuclear and cell division. Citation Format: Chieh-Ting Fang, Hsiao-Hui Kuo, Sih-Long Liu, Jhong-Syuan Yao, Ling-Huei Yih. Inhibition of acetyl-CoA carboxylase induced spindle abnormalities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1573.