Oxygen regulation of breathing is abolished in mitochondrial complex III-deficient arterial chemoreceptors.
Daniel Cabello-RiveraPatricia Ortega-SáenzLin GaoAna M Muñoz-CabelloVictoria Bonilla-HenaoPaul T SchumackerJosé López-BarneoPublished in: Proceedings of the National Academy of Sciences of the United States of America (2022)
Acute oxygen (O 2 ) sensing is essential for adaptation of organisms to hypoxic environments or medical conditions with restricted exchange of gases in the lung. The main acute O 2 -sensing organ is the carotid body (CB), which contains neurosecretory chemoreceptor (glomus) cells innervated by sensory fibers whose activation by hypoxia elicits hyperventilation and increased cardiac output. Glomus cells have mitochondria with specialized metabolic and electron transport chain (ETC) properties. Reduced mitochondrial complex (MC) IV activity by hypoxia leads to production of signaling molecules (NADH and reactive O 2 species) in MCI and MCIII that modulate membrane ion channel activity. We studied mice with conditional genetic ablation of MCIII that disrupts the ETC in the CB and other catecholaminergic tissues. Glomus cells survived MCIII dysfunction but showed selective abolition of responsiveness to hypoxia (increased [Ca 2+ ] and transmitter release) with normal responses to other stimuli. Mitochondrial hypoxic NADH and reactive O 2 species signals were also suppressed. MCIII-deficient mice exhibited strong inhibition of the hypoxic ventilatory response and altered acclimatization to sustained hypoxia. These data indicate that a functional ETC, with coupling between MCI and MCIV, is required for acute O 2 sensing. O 2 regulation of breathing results from the integrated action of mitochondrial ETC complexes in arterial chemoreceptors.
Keyphrases
- induced apoptosis
- oxidative stress
- liver failure
- cell cycle arrest
- endothelial cells
- respiratory failure
- healthcare
- cell death
- gene expression
- endoplasmic reticulum stress
- drug induced
- palliative care
- heart failure
- signaling pathway
- metabolic syndrome
- machine learning
- electronic health record
- intensive care unit
- hepatitis b virus
- multidrug resistant
- radiofrequency ablation
- acute respiratory distress syndrome
- wild type
- atrial fibrillation
- genetic diversity
- electron transfer