Back to Search
Start Over
Upregulation of COX4-2 via HIF-1α in Mitochondrial COX4-1 Deficiency
- Source :
- Cells, Vol 10, Iss 2, p 452 (2021)
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- Cytochrome-c-oxidase (COX) subunit 4 (COX4) plays important roles in the function, assembly and regulation of COX (mitochondrial respiratory complex 4), the terminal electron acceptor of the oxidative phosphorylation (OXPHOS) system. The principal COX4 isoform, COX4-1, is expressed in all tissues, whereas COX4-2 is mainly expressed in the lungs, or under hypoxia and other stress conditions. We have previously described a patient with a COX4-1 defect with a relatively mild presentation compared to other primary COX deficiencies, and hypothesized that this could be the result of a compensatory upregulation of COX4-2. To this end, COX4-1 was downregulated by shRNAs in human foreskin fibroblasts (HFF) and compared to the patient’s cells. COX4-1, COX4-2 and HIF-1α were detected by immunocytochemistry. The mRNA transcripts of both COX4 isoforms and HIF-1 target genes were quantified by RT-qPCR. COX activity and OXPHOS function were measured by enzymatic and oxygen consumption assays, respectively. Pathways were analyzed by CEL-Seq2 and by RT-qPCR. We demonstrated elevated COX4-2 levels in the COX4-1-deficient cells, with a concomitant HIF-1α stabilization, nuclear localization and upregulation of the hypoxia and glycolysis pathways. We suggest that COX4-2 and HIF-1α are upregulated also in normoxia as a compensatory mechanism in COX4-1 deficiency.
- Subjects :
- mitochondria
cytochrome c oxidase
COX4-1
COX4-2
HIF-1α
Cytology
QH573-671
Subjects
Details
- Language :
- English
- ISSN :
- 20734409
- Volume :
- 10
- Issue :
- 2
- Database :
- Directory of Open Access Journals
- Journal :
- Cells
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.241985c434a546a295baaf9d6479675c
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/cells10020452