Abstract 3043: Discovery of a novel mitochondrial protein complex containing pro-apoptotic Noxa in leukemia

Abstract

Abstract Apoptosis evasion and altered nutrient metabolism are recognized as major contributors to cancer development. However, the degree to which apoptosis and metabolism are integrated in malignant cells remains poorly understood. Previously our group observed alterations in mitochondrial function mediated by expression of the pro-apoptotic member of the Bcl-2 family Noxa. Here, we report the presence of a large 650 kilodalton multi-protein complex specific to the mitochondria of Jurkat leukemia cells that contains Noxa. We also detect a similar mitochondrial protein complex in cells expressing Noxa with a mutated BH3 domain, suggestive of an apoptosis-independent metabolic function for this Bcl-2 family member. Lastly, we present here the successful isolation of this complex aimed at identifying other complex components via mass spectrometry. This unique strategy included purifying the complex by gel-filtration chromatography, and then resolving the complex into an acrylamide gel by either size or charge, followed by separating the individual complex components by size. Future studies are geared towards identifying the other components of the complex, looking for presence of this complex in other cancers, and understanding how this complex may function in maintaining mitochondrial homeostasis in cancer. In summary, the data presented here strongly suggests a non-canonical function for Noxa in regulating mitochondrial function independent of apoptosis in leukemia, and possibly other malignancies. Note: This abstract was not presented at the meeting. Citation Format: Jeffrey S. Gaynes, Eric A. Hanse, Ameeta Kelekar. Discovery of a novel mitochondrial protein complex containing pro-apoptotic Noxa in leukemia. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3043. doi:10.1158/1538-7445.AM2015-3043