The OXPHOS supercomplex assembly factor HIG2A responds to changes in energetic metabolism and cell cycle |
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| Authors: | Celia Salazar Alvaro A. Elorza Glenda Cofre Paula Ruiz-Hincapie Orian Shirihai Lina María Ruiz |
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| Affiliation: | 1. Instituto de Ciencias Biomédicas, Facultad Ciencias de la Salud, Universidad Autónoma de Chile, Santiago, Chile;2. Institute of Biomedical Sciences, Faculty of Medicine and Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile Millennium Institute of Immunology and Immunotherapy, Santiago, Chile;3. School of Engineering and Technology, University of Hertfordshire, Hatfield, UK;4. Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California |
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| Abstract: | 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 (ΔΨm) 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. |
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| Keywords: | cell cycle E2F1 HIG2A hypoxia mitochondrial dynamics OPA1 OXPHOS supercomplexes |
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