Non-canonical hemoglobin: An updated review on its ubiquitous expression

Hemoglobin, once thought to be exclusive to erythrocytes, has been identified to be expressed in various cell types over the past several decades. While hemoglobin's function within erythrocytes is primarily characterized as a gaseous transport molecule, its function within non-erythrocyte cell...

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Main Authors: Emily C. Reed, Jacob D. Kim, Adam J. Case
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Redox Biology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2213231725001156
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author Emily C. Reed
Jacob D. Kim
Adam J. Case
author_facet Emily C. Reed
Jacob D. Kim
Adam J. Case
author_sort Emily C. Reed
collection DOAJ
description Hemoglobin, once thought to be exclusive to erythrocytes, has been identified to be expressed in various cell types over the past several decades. While hemoglobin's function within erythrocytes is primarily characterized as a gaseous transport molecule, its function within non-erythrocyte cells varies among different cell types, and in many cases, remains to be fully elucidated. Despite this variability, hemoglobin expression seems to broadly function as a redox modulator, whether it is involved in the hypoxic response, mitochondrial function, antioxidant balance or, like in erythrocytes, gas transport. This review provides an updated summary of the most recent discoveries of hemoglobin in non-erythrocyte cells. While discussing the function and regulation of this ubiquitous protein, we additionally compare these cell-specific details to identify commonalities throughout the diverse group of hemoglobin-expressing cells. Lastly, we discuss potential implications of non-canonical hemoglobin in various disease states such neurodegeneration, autoimmune disorders, psychological trauma, and hemoglobinopathies, while providing future directions for hemoglobin research.
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spelling doaj-art-287eb5db52154db3bc8be790616d805c2025-08-20T03:14:52ZengElsevierRedox Biology2213-23172025-05-018210360210.1016/j.redox.2025.103602Non-canonical hemoglobin: An updated review on its ubiquitous expressionEmily C. Reed0Jacob D. Kim1Adam J. Case2Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX, United States; Department of Medical Physiology, Texas A&M University, Bryan, TX, United StatesProsper High School, Prosper, TX, United StatesDepartment of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX, United States; Department of Medical Physiology, Texas A&M University, Bryan, TX, United States; Corresponding author. Department of Psychiatry and Behavioral Sciences, Department of Medical Physiology, 8447 John Sharp Pkwy, MREB2 3414, Bryan, TX 77807, United States. acase@tamu.eduHemoglobin, once thought to be exclusive to erythrocytes, has been identified to be expressed in various cell types over the past several decades. While hemoglobin's function within erythrocytes is primarily characterized as a gaseous transport molecule, its function within non-erythrocyte cells varies among different cell types, and in many cases, remains to be fully elucidated. Despite this variability, hemoglobin expression seems to broadly function as a redox modulator, whether it is involved in the hypoxic response, mitochondrial function, antioxidant balance or, like in erythrocytes, gas transport. This review provides an updated summary of the most recent discoveries of hemoglobin in non-erythrocyte cells. While discussing the function and regulation of this ubiquitous protein, we additionally compare these cell-specific details to identify commonalities throughout the diverse group of hemoglobin-expressing cells. Lastly, we discuss potential implications of non-canonical hemoglobin in various disease states such neurodegeneration, autoimmune disorders, psychological trauma, and hemoglobinopathies, while providing future directions for hemoglobin research.http://www.sciencedirect.com/science/article/pii/S2213231725001156HemoglobinHbαHbβReactive oxygen speciesMitochondriaRedox
spellingShingle Emily C. Reed
Jacob D. Kim
Adam J. Case
Non-canonical hemoglobin: An updated review on its ubiquitous expression
Redox Biology
Hemoglobin
Hbα
Hbβ
Reactive oxygen species
Mitochondria
Redox
title Non-canonical hemoglobin: An updated review on its ubiquitous expression
title_full Non-canonical hemoglobin: An updated review on its ubiquitous expression
title_fullStr Non-canonical hemoglobin: An updated review on its ubiquitous expression
title_full_unstemmed Non-canonical hemoglobin: An updated review on its ubiquitous expression
title_short Non-canonical hemoglobin: An updated review on its ubiquitous expression
title_sort non canonical hemoglobin an updated review on its ubiquitous expression
topic Hemoglobin
Hbα
Hbβ
Reactive oxygen species
Mitochondria
Redox
url http://www.sciencedirect.com/science/article/pii/S2213231725001156
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