The OXPHOS Supercomplex Assembly Factor HIG2A Responds to Changes in Energetic Metabolism and Cell Cycle

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The OXPHOS supercomplex assembly factor HIG2A responds to changes in energetic metabolism and cell cycle Salazar C. Elorza A.A. Cofre G. Ruiz-Hincapie P. Shirihai O. Ruiz L.M. HIG2A promotes cell survival under hypoxia and mediates the assembly of complex III and complex IV into respiratory chain supercomplexes. In the present study, we show that human HIGD2A and mouse Higd2a gene expressions are regulated by hypoxia, glucose, and the cell cycle-related transcription factor E2F1. The latter was found to bind the promoter region of HIGD2A. Differential expression of the HIGD2A gene was found in C57BL/6 mice in relation to tissue and age. Besides, the silencing of HIGD2A evidenced the modulation of mitochondrial dynamics proteins namely, OPA1 as a fusion protein increases, while FIS1, a fission protein, decreases. Besides, the mitochondrial membrane potential (??m) increased. The protein HIG2A is localized in the mitochondria and nucleus. Moreover, we observed that the HIG2A protein interacts with OPA1. Changes in oxygen concentration, glucose availability, and cell cycle regulate HIGD2A expression. Alterations in HIGD2A expression are associated with changes in mitochondrial physiology. © 2019 Wiley Periodicals, Inc. cell cycle E2F1 HIG2A hypoxia mitochondrial dynamics OPA1 OXPHOS supercomplexes cytochrome c oxidase glucose RNA directed DNA polymerase transcription factor E2F1 ubiquinol cytochrome c reductase HIG2 protein, mouse HILPDA protein, human mitochondrial protein reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) tumor protein animal experiment animal model animal tissue Article cell cycle cell hypoxia cell survival controlled study energy metabolism gene gene expression HEK293 cell line higd2a gene immunofluorescence immunoprecipitation male mitochondrial dynamics mitochondrial membrane potential mitochondrion mouse neuroblastoma cell nonhuman oxidative phosphorylation oxidative phosphorylation system oxygen concentration priority journal promoter region real time polymerase chain reaction respiratory chain Western blotting animal C57BL mouse cell cycle genetics human metabolism mitochondrial membrane physiology Animals Cell Cycle Electron Transport Complex I Humans Membrane Potential, Mitochondrial Mice, Inbred C57BL Mitochondrial Dynamics Mitochondrial Membranes Mitochondrial Proteins Neoplasm Proteins.

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