Truncated Hemoglobin O Carries an Autokinase Activity and Facilitates Adaptation of Under Hypoxia.

Hade, Mangesh Dattu and Sethi, Deepti and Datta, Himani and Singh, Sandeep and Thakur, Naveen and Chhaya, Ajay and Dikshit, Kanak L (2020) Truncated Hemoglobin O Carries an Autokinase Activity and Facilitates Adaptation of Under Hypoxia. Antioxidants & redox signaling, 32 (6). pp. 351-362. ISSN 1557-7716

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Although the human pathogen, (), is strictly aerobic and requires efficient supply of oxygen, it can survive long stretches of severe hypoxia. The mechanism responsible for this metabolic flexibility is unknown. We have investigated a novel mechanism by which hemoglobin O (HbO), operates and supports its host under oxygen stress. We discovered that the HbO exists in a phospho-bound state in and remains associated with the cell membrane under hypoxia. Deoxy-HbO carries an autokinase activity that disrupts its dimeric assembly into monomer and facilitates its association with the cell membrane, supporting survival and adaptation of under low oxygen conditions. Consistent with these observations, deletion of the O gene in bacillus Calmette-Guerin, which is identical to the O gene of , attenuated its survival under hypoxia and complementation of the O gene of rescued this inhibition, but phosphorylation-deficient mutant did not. These results demonstrated that autokinase activity of the HbO modulates its physiological function and plays a vital role in supporting the survival of its host under hypoxia. Our study demonstrates that the redox-dependent autokinase activity regulates oligomeric state and membrane association of HbO that generates a reservoir of oxygen in the proximity of respiratory membranes to sustain viability of under hypoxia. These results thus provide a novel insight into the physiological function of the HbO and demonstrate its pivotal role in supporting the survival and adaptation of under hypoxia.

Item Type: Article
Additional Information: Copyright of this article belongs to Mary Ann Liebert, Inc.
Uncontrolled Keywords: HbO; Mycobacterium tuberculosis; autophosphorylation; hypoxia; truncated hemoglobin
Subjects: Q Science > QR Microbiology
Depositing User: Dr. K.P.S.Sengar
Date Deposited: 26 Feb 2020 15:02
Last Modified: 26 Feb 2020 15:02

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