title: Altered mitochondrial biogenesis and its fusion gene expression is involved in the high-altitude adaptation of rat lung.
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.
authors.affiliation: Molecular Biology and Biotechnology Division, DRDO - BU Center for Life Sciences, Bharathiar University, Coimbatore 641 046, Tamil Nadu, India.
authors.forename: Loganathan
authors.initials: L
authors.lastname: Chitra
authors.affiliation: Department of Biotechnology, Bharathiar University, Coimbatore 641 046, Tamil Nadu, India. Electronic address: boopathybiotech@gmail.com.
authors.forename: Rathanam
authors.initials: R
authors.lastname: Boopathy
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000531:Altitude; D000818:Animals; D002950:Citrate (si)-Synthase; D004272:DNA, Mitochondrial / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D000860:Hypoxia / Q000503:physiopathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000502:physiology*; D008297:Male; D063269:Mitochondrial Turnover / Q000502:physiology*; D009243:NAD / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D011654:Pulmonary Edema / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D009243:NAD; D007770:L-Lactate Dehydrogenase; D002950:Citrate (si)-Synthase
keywords: ATP synthetase6/8; ATP6/8; CO I/II/III; CS; Cyt b; Drp-1; ERRα; Estrogen-related receptor-α; Fis1; HH; IHH; Intermittent hypobaric hypoxia; Mfn1/2; Mitochondrial biogenesis; Mitofusin-2; NADH-dehydrogenase-ubiquinone reductase1 to 6* 4L; ND1 to 6* 4L; NRF1/2; OXPHOS; Oxidative phosphorylation; PC; PGC-1α; RNS; ROS; TFAM; citrate synthase; cytochrome b; cytochrome c oxidase I/II/III; dynamin-related protein-1; estrogen-related receptor-α; hypobaric hypoxia; intermittent hypobaric hypoxia; mitochondrial DNA; mitochondrial transcription factor A; mitofusin1/2; mtDNA; nDNA; nuclear DNA; nuclear respiratory factor 1/2; oxidative phosphorylation; peroxisome proliferator-activated receptor-γ coactivator-1α; preconditioning; reactive nitrogen species; reactive oxygen species; ﬁssion 1