Timon-Gomez 2022 Elife
TimΓ³n-GΓ³mez A, Scharr AL, Wong NY, Ni E, Roy A, Liu M, Chau J, Lampert JL, Hireed H, Kim NS, Jan M, Gupta AR, Day RW, Gardner JM, Wilson RJA, Barrientos A, Chang AJ (2022) Tissue-specific mitochondrial HIGD1C promotes oxygen sensitivity in carotid body chemoreceptors. https://doi.org/10.7554/elife.78915 |
Β» Elife 11:e78915. PMID: 36255054 Open Access
Timon-Gomez Alba, Scharr Alexandra L, Wong Nicholas Y, Ni Erwin, Roy Arijit, Liu Min, Chau Julisia, Lampert Jack L, Hireed Homza, Kim Noah S, Jan Masood, Gupta Alexander R, Day Ryan W, Gardner James M, Wilson Richard JA, Barrientos Antoni, Chang Andy J (2022) Elife
Abstract: Mammalian carotid body arterial chemoreceptors function as an early warning system for hypoxia, triggering acute life-saving arousal and cardiorespiratory reflexes. To serve this role, carotid body glomus cells are highly sensitive to decreases in oxygen availability. While the mitochondria and plasma membrane signaling proteins have been implicated in oxygen sensing by glomus cells, the mechanism underlying their mitochondrial sensitivity to hypoxia compared to other cells is unknown. Here, we identify HIGD1C, a novel hypoxia-inducible gene domain factor isoform, as an electron transport chain complex IV-interacting protein that is almost exclusively expressed in the carotid body and is therefore not generally necessary for mitochondrial function. Importantly, HIGD1C is required for carotid body oxygen sensing and enhances complex IV sensitivity to hypoxia. Thus, we propose that HIGD1C promotes exquisite oxygen sensing by the carotid body, illustrating how specialized mitochondria can be used as sentinels of metabolic stress to elicit essential adaptive behaviors. β’ Keywords: Biochemistry, Carotid body, Chemical biology, Human, Mitochondria, Mouse, Neuroscience, Oxygen sensing, Rat β’ Bioblast editor: Plangger M β’ O2k-Network Lab: US FL Miami Barrientos A
Preprint
Labels: MiParea: Respiration, Genetic knockout;overexpression
Stress:Hypoxia
Preparation: Permeabilized cells, Intact cells
Enzyme: Complex IV;cytochrome c oxidase
Pathway: CIV
HRR: Oxygraph-2k
2023-06