Abstract: Depression is a common mental illness with mood disorders as the main clinical feature. In recent years numerous studies have shown that mitochondrial function and structure are abnormal in patients with depression, and changes in mitochondrial ultrastructure can lead to energy metabolism disorders in the body. It is suggested that ‘mitochondrial energy metabolism disorder’ may be the pathogenesis of depression. This paper reviews the intrinsic association of mitochondrial energy metabolism with depression and notes potential mechanisms from the standpoint of mitochondrial structure and function on the molecular level. We provide a reference for understanding the pathogenesis of depression and identifying the possible targets of antidepressant drugs.