Abstract 2409: The effect of heme on mitochondrial biogenesis and function of NSCLC cells

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Abstract Heme is a central molecule for mitochondrial function and for many processes involved in oxygen utilization. Heme serves as a prosthetic group or a cofactor for a number of oxidative phosphorylation enzymes and other oxygen-utilizing hemoproteins. Heme also directly regulates the synthesis, translocation, and assembly of these enzyme complexes. Most, if not all, human cells can synthesize and uptake heme from the circulation. A number of epidemiologic studies have shown that high heme intake is associated with increased risk of cancer, including lung cancer. To assess the status of heme metabolism in lung cancer cells, we performed a series of experiments in non-small cell lung cancer (NSCLC) cell lines and compared the results with an immortalized normal lung cell line, HBEC30KT. We observed significant increase in rates of heme synthesis and heme uptake in NSCLC cells compared to HBEC30KT. Previous studies carried out in our lab showed intensified mitochondrial respiration and increased levels of heme as well as hemoproteins in NSCLCs. NSCLCs were also found to exhibit significantly high expressions of proteins involved in mitochondrial biogenesis such as SIRT-1, PGC1α, NRF-1, NRF-2, and TFAM. Expression levels of these proteins correlate with oxygen consumption and total heme content in NSCLCs, suggesting a possibility of role of heme in mitochondrial biogenesis. Immunofluoresence studies showed that heme depletion and add-back significantly affected localization and expression levels of these proteins. Studies are currently under way to determine how heme depletion affects the interactions of various transcription factors involved in mitochondrial biogenesis and function. Citation Format: Sagar Shashikant Sohoni, Chantal Vidal, Li Zhang. The effect of heme on mitochondrial biogenesis and function of NSCLC cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2409.