ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2023
Unique expression of the atypical mitochondrial subunit NDUFA4L2 in cerebral pericytes fine tunes HIF activity in response to hypoxia.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed, 10 citations in OpenAlex.
- An integrated spatially defined roadmap of normal and cancer-associated colon fibroblasts.Molecular systems biology · 2026Article
- COXFA4L2 upregulation preserves residual cytochrome c oxidase activity in COXFA4-related Leigh-like encephalopathy.Nature communications · 2026Article
- Cis-regulatory evolution reveals sensory trade-offs as a genetic basis for temporal niche evolution in tapirs.Science advances · 2026Article
- Tumor-Associated Pericytes: Tumorigenicity and Targeting for Cancer Therapy.Current vascular pharmacology · 2026Review
- Single-cell transcriptomics of clinical grade adipose-derived regenerative cells reveals consistency between donors independent of gender and BMI.Stem cell research & therapy · 2025Article
- Pericytes in Glioblastoma: Hidden Regulators of Tumor Vasculature and Therapy Resistance.Cancers · 2024Review
- Biology of vascular mural cells.Development (Cambridge, England) · 2023Review
- Integrative analysis deciphers the heterogeneity of cancer-associated fibroblast and implications on clinical outcomes in ovarian cancers.Computational and structural biotechnology journal · 2022Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A central response to insufficient cerebral oxygen delivery is a profound reprograming of metabolism, which is mainly regulated by the Hypoxia Inducible Factor (HIF). Among other responses, HIF induces the expression of the atypical mitochondrial subunit NDUFA4L2. Surprisingly, NDUFA4L2 is constitutively expressed in the brain in non-hypoxic conditions. Analysis of publicly available single cell transcriptomic (scRNA-seq) data sets coupled with high-resolution multiplexed fluorescence RNA in situ hybridization (RNA F.I.S.H.) revealed that in the murine and human brain NDUFA4L2 is exclusively expressed in mural cells with the highest levels found in pericytes and declining along the arteriole-arterial smooth muscle cell axis. This pattern was mirrored by COX4I2, another atypical mitochondrial subunit. High NDUFA4L2 expression was also observed in human brain pericytes in vitro, decreasing when pericytes are muscularized and further induced by HIF stabilization in a PHD2/PHD3 dependent manner. In vivo,
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