The OXPHOS supercomplex assembly factor HIG2A responds to changes in energetic metabolism and cell cycle

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 fact...

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Published in:Journal of cellular physiology 2019-10, Vol.234 (10), p.17405-17419
Main Authors: Salazar, Celia, Elorza, Alvaro A., Cofre, Glenda, Ruiz‐Hincapie, Paula, Shirihai, Orian, Ruiz, Lina María
Format: Article
Language:English
Subjects:
Animal tissues
Assembly
Cell cycle
Cell survival
E2F1
Electron transport
Fusion protein
Gene expression
Glucose
HIG2A
Hypoxia
Membrane potential
Metabolism
Mitochondria
mitochondrial dynamics
OPA1
OXPHOS supercomplexes
Proteins
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Summary: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. Transcriptional regulation of HIGD2A might function as a regulator of respiratory supercomplexes assembly in response to hypoxia, cellular metabolism, and cell cycle.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.28362