Genetic and metabolic responses of mitochondria under hypobaric hypoxia at high altitude in Indian population

Abstract

The present study demonstrated the role of mitochondrial DNA mutations, haplogroups as well as metabolic reprogramming in response to hypobaric hypoxia environment at high altitude in Indian male subjects including, HAPE subjects, acclimatized controls and high altitude Ladakhi natives. This study summarizes that exposure to high altitude increases oxidative stress in sea level individuals subjected to high altitude and the mtDNA mutations in OXPHOS complex genes increased the production of ROS thereby enhancing the mitophagy and reducing the mitochondrial biogenesis in an HIF dependent manner, resulting in decreased mitochondrial density and metabolic reprogramming in HAPE subjects. The putatively advantageous mtDNA mutations in Ladakhi natives showed an adaptive response to high altitude. This study provides important clues to understand the pathophysiology of HAPE and other altitude disorders as well as the mechanism of adaptation in high altitude Ladakhi natives. newline