A high altitude plateau is a unique environment with low pressure, oxygen, and temperature. The plateau environment reduces the metabolism of energy substances and mitochondrial functions, thereby affecting work on a plateau. In recent years, mitochondrial damage has attracted broad attention. As the energy factory of cells, mitochondria are closely linked to body movement. We focused our attention on mitochondrial damage at high altitude and summarized the effects of high altitude on the metabolism of basic energy substances and changes in important enzyme activities and the mitochondrial structure and function in the mitochondrial biochemical energy supply response. We found that protein, carbohydrate and lipid metabolism was negatively affected at high altitude, resulting in fatigue, hyperlipidemia, and body repair. The activities of enzymes related to pyruvate metabolism, the tricarboxylic acid cycle, β-oxidation, and oxidative phosphorylation were inhibited, and the morphology and number of mitochondria were changed, leading to impaired mitochondrial functions and affecting exercise energy supply. Exploration of the mechanism of cell injury at high altitude may promote research to prevent and treat such injuries.