Increased BNIP3 activity contributes to mitochondrial dysregulation: A hypothesis on the mechanism of ineffective erythropoiesis in β-thalassemia
Issued Date
2024-08-01
Resource Type
ISSN
03069877
eISSN
15322777
Scopus ID
2-s2.0-85195066504
Journal Title
Medical Hypotheses
Volume
189
Rights Holder(s)
SCOPUS
Bibliographic Citation
Medical Hypotheses Vol.189 (2024)
Suggested Citation
Noulsri E., Lerdwana S. Increased BNIP3 activity contributes to mitochondrial dysregulation: A hypothesis on the mechanism of ineffective erythropoiesis in β-thalassemia. Medical Hypotheses Vol.189 (2024). doi:10.1016/j.mehy.2024.111395 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/98677
Title
Increased BNIP3 activity contributes to mitochondrial dysregulation: A hypothesis on the mechanism of ineffective erythropoiesis in β-thalassemia
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Author's Affiliation
Corresponding Author(s)
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Abstract
Ineffective erythropoiesis (IE) and the premature destruction of erythroblasts play important roles in the pathophysiology of β-thalassemia. Accumulating evidence suggests that the pathology of IE is associated with multiple factors, including apoptosis and reactive oxygen species (ROS) generation. A previous study also indicated that dysregulation of mitochondrial homeostasis and autophagy contributes to IE in the bone marrow of β-thalassemia patients. However, the precise molecular mechanism underlying mitochondria-mediated IE remains poorly understood. Here, we propose that the increased activity of adenovirus E1B 19-kDa-interacting protein 3 (BNIP3) promotes mitochondrial fragmentation, autophagy, and apoptosis of erythroid progenitors in β-thalassemia. The present hypothesis is based on the published literature showing that 1) BNIP3 is involved in mitochondrial dysfunction and autophagy, 2) BNIP3 expression is regulated by p53 and hypoxia-inducible factor-1α, and 3) BNIP3 expression can be attenuated by a number of approaches. Our hypothesis can be verified through both in vitro and in vivo experiments. BNIP3 could be a promising therapeutic target for minimizing the pathophysiology of IE and reducing ROS generation associated with mitochondrial dysfunction in patients with β-thalassemia.