| First Author | Reed EC | Year | 2025 |
| Journal | Free Radic Biol Med | Volume | 227 |
| Pages | 1-11 | PubMed ID | 39586383 |
| Mgi Jnum | J:361016 | Mgi Id | MGI:7855103 |
| Doi | 10.1016/j.freeradbiomed.2024.11.044 | Citation | Reed EC, et al. (2024) Hemoglobin alpha is a redox-sensitive mitochondrial-related protein in T-lymphocytes. Free Radic Biol Med 227:1-11 |
| abstractText | Hemoglobin subunits, which form the well-characterized, tetrameric, oxygen-carrying protein, have recently been described to be expressed in various non-canonical cell types. However, the exact function of hemoglobin subunits within these cells remains to be fully elucidated. Herein, we report for the first time, the expression of hemoglobin alpha-a1 (Hba-a1) in T-lymphocytes and describe its role as a mitochondrial-associated antioxidant. Within naive T-lymphocytes, Hba-a1 mRNA and HBA protein are present and highly induced by redox perturbations, particularly those arising from the mitochondria. Additionally, preliminary data using a T-lymphocyte specific Hba-a1 knock-out mouse model indicated that the loss of Hba-a1 led to an exacerbated production of mitochondrial reactive oxygen species and inflammatory cytokines after a stress challenge, further supporting the role of HBA acting to buffer the mitochondrial redox environment. Interestingly, we observed Hba-a1 expression to be significantly upregulated or downregulated depending on T-lymphocyte polarization and metabolic state, which appeared to be controlled by both transcriptional regulation and chromatin remodeling. Altogether, these data suggest Hba-a1 may function as a crucial mitochondrial-associated antioxidant and appears to possess critical and complex functions related to T-lymphocyte activation and differentiation. |
