ArticleProceedings of the National Academy of Sciences of the United States of America2015
Higd1a is a positive regulator of cytochrome c oxidase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 129 citations in OpenAlex.
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- Experience-mediated transcriptional memory correlates with hypoxia resistance in the nervous system of the sea hareAmerican journal of physiology. Regulatory, integrative and comparative physiology · 2025Article
- The Role of Mitochondria in Obstructive Sleep Apnea: Implications for the Upper Airway Muscles.International journal of molecular sciences · 2025Review
- The potential antitumor mechanism and clinical potential of Higd-1a in colorectal cancer.Scientific reports · 2025Article
- HIGD1A Alleviates Oxidative Stress Related Ovarian Hypofunction by Enhancing Granulosa Cell Functions via NF-κB/SOD2 Signaling Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Bioinformatics insights into mitochondrial and immune gene regulation in Alzheimer's disease.European journal of medical research · 2025Article
- The flexible chain: regulation of structure and activity of ETC complexes defines rate of ATP synthesis and sites of superoxide generation.Biophysical reviews · 2025Review
- Procyanidin C1 inhibits tumor growth and metastasis in colon cancer via modulating miR-501-3p/HIGD1A axis.Journal of advanced research · 2024Article
- Mitochondrial respiratory chain component NDUFA4: a promising therapeutic target for gastrointestinal cancer.Cancer cell international · 2024Review
- Genomic insights into the population history and adaptive traits of Latin American Criollo cattle.Royal Society open science · 2024Article
- Cytochrome c oxidase subunit I gene in Thalassiosira nordenskioeldii strains inhabiting in cold and warm sea waters.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2024Article
- Proton Compared to X-Irradiation Induces Different Protein Profiles in Oral Cancer Cells and Their Derived Extracellular Vesicles.International journal of molecular sciences · 2023Article
- Review
- Mitochondrial Factors in the Cell Nucleus.International journal of molecular sciences · 2023Review
- The functional role of Higd1a in mitochondrial homeostasis and in multiple disease processes.Genes & diseases · 2023Review
- Cryo-EM structure and function of S. pombe complex IV with bound respiratory supercomplex factor.Communications chemistry · 2023Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytochrome c oxidase (CcO) is the only enzyme that uses oxygen to produce a proton gradient for ATP production during mitochondrial oxidative phosphorylation. Although CcO activity increases in response to hypoxia, the underlying regulatory mechanism remains elusive. By screening for hypoxia-inducible genes in cardiomyocytes, we identified hypoxia inducible domain family, member 1A (Higd1a) as a positive regulator of CcO. Recombinant Higd1a directly integrated into highly purified CcO and increased its activity. Resonance Raman analysis revealed that Higd1a caused structural changes around heme a, the active center that drives the proton pump. Using a mitochondria-targeted ATP biosensor, we showed that knockdown of endogenous Higd1a reduced oxygen consumption and subsequent mitochondrial ATP synthesis, leading to increased cell death in response to hypoxia; all of these phenotypes were rescued by exogenous Higd1a. These results suggest that Higd1a is a previously unidentified regulatory component of CcO, and represents a therapeutic target for diseases associated with reduced CcO activity.
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