{'fraction_non_alphanumeric': 0.01460446247464503, 'fraction_numerical': 0.0012170385395537525, 'mean_word_length': 6.339285714285714, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Altered Metabolism and Mitochondrial Lipid Content Drive the Evasion of Apoptosis

Mitochondria are the metabolic centers of the cell and critical players in initiating programmed cell death. Mitochondrial dysfunction and dysregulated apoptosis contribute to a number of disease states, including inherited mitochondrial syndromes, neurological disorders, and cancer. Critical to both mitochondrial function and apoptosis is the architecture of mitochondrial membranes. A mitochondrion is comprised of an inner and outer membrane composed of numerous phospholipids, including cardiolipin, a phospholipid found exclusively in the mitochondria. Cardiolipin binds to cytochrome c in the inner mitochondrial membrane, preventing its release and the initiation of intrinsic apoptosis. Defects in genes required for the maintenance of mitochondrial membrane structure and cardiolipin composition have been identified, and represent an emerging class of mitochondrial disorders. However, a detailed molecular understanding of the synthesis and regulation of mitochondrial membrane phospholipids is lacking. The overall objective is to investigate mechanisms of increased cardiolipin biosynthesis and to study the role of cardiolipin content and composition in regulating the initiation of intrinsic apoptosis. Cancer cells are often characterized by an increased dependence on glucose. These cancers are often resistant to chemotherapies, representing a significant clinical problem. Current research employing cellular phospholipid quantitation has identified that altered cellular glucose metabolism regulates cardiolipin synthesis. Further, the effects of altered cardiolipin levels on cell viability and cytochrome c release upon RNA mediated knockdown of cardiolipin biosynthesis enzymes were studied. Data acquired from cell viability and immunofluorescence microscopy assays suggest that knockdown of cardiolipin synthase (CRLS1), resulting in decreased cardiolipin levels, decreased cell viability after drug treatment, and increased cytochrome c release. Alternatively, loss of lysophosphatidic acid phosphatase type 6 (ACP6), hypothesized to increase cardiolipin levels, resulted in decreased cytochrome c release, which increased cell viability. These results will allow for an increased fundamental understanding of cardiolipin physiology in order to uncover the therapeutic potential of targeting new mitochondrial pathways to treat human disease like cancer.