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Title: Altered mitochondrial biogenesis and its fusion gene expression is involved in the high-altitude adaptation of rat lung. Author: Chitra L, Boopathy R. Journal: Respir Physiol Neurobiol; 2014 Feb 01; 192():74-84. PubMed ID: 24361501. Abstract: Intermittent hypobaric hypoxia-induced preconditioning (IHH-PC) of rat favored the adaption of lungs to severe HH conditions, possibly through stabilization of mitochondrial function. This is based on the data generated on regulatory coordination of nuclear DNA-encoded mitochondrial biogenesis; dynamics, and mitochondrial DNA (mtDNA)-encoded oxidative phosphorylation (mtOXPHOS) genes expression. At 16th day after start of IHH-PC (equivalent to 5000m, 6h/d, 2w of treatment), rats were exposed to severe HH stimulation at 9142m for 6h. The IHH-PC significantly counteracted the HH-induced effect of increased lung: water content; tissue damage; and oxidant injury. Further, IHH-PC significantly increased the mitochondrial number, mtDNA content and mtOXPHOS complex activity in the lung tissues. This observation is due to an increased expression of genes involved in mitochondrial biogenesis (PGC-1α, ERRα, NRF1, NRF2 and TFAM), fusion (Mfn1 and Mfn2) and mtOXPHOS. Thus, the regulatory pathway formed by PGC-1α/ERRα/Mfn2 axes is required for the mitochondrial adaptation provoked by IHH-PC regimen to counteract subsequent HH stress.[Abstract] [Full Text] [Related] [New Search]