The study of GRIM-19 function in mitochondria

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.