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Title: The study of GRIM-19 function in mitochondria
Authors: LU HAO
Keywords: GRIM-19, mitochondria, membrane potential , domain, complex I, apoptosis
Issue Date: 26-Sep-2008
Citation: LU HAO (2008-09-26). The study of GRIM-19 function in mitochondria. ScholarBank@NUS Repository.
Abstract: Mitochondria play essential roles in cellular energy production via mitochondrial respiratory chain (RC). NADH:ubiquinone oxidoreductase (complex I) is the largest complex that catalyzes the first step of electron transport of RC. The relationship between GRIM-19 and complex I was not clear. This study clearly demonstrated that GRIM-19 is a subunit of mitochondrial complex I by showing: (1) GRIM-19 interacted with various mitochondrial complex I subunits and was physically present in mitochondrial complex I. (2) In GRIM-19 knockout mice, mitochondrial complex I holoenzyme could not be fully assembled and complex I activity was totally abolished, which indicated that GRIM-19 is essential for complex I assembly and enzymatic activity. In addition, several important functional domains in GRIM-19 were identified. The mitochondrial localization sequences were defined at the N-terminal, the electron transfer activity domain was found in the middle and the last 10 amino acid at C-terminal enhanced the assembly ability of GRIM-19 to complex I. Based on the domains mapping information, a dominant-negative GRIM-19, which can specifically decrease mitochondrial membrane potential, was generated. In summary, this study clearly demonstrated that GRIM-19 was a crucial subunit in mitochondrial complex I.
Appears in Collections:Ph.D Theses (Open)

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