Metabolic Reprogramming of Human Cells in Response to Oxidative Stress: Implications in the Pathophysiology and Therapy of Mitochondrial Diseases

In this regard, we review recent findings to elucidate the mechanisms by which human cells motivate their mitochondria and theantioxidant defense system to respond to energy deficiency and oxidative stress, which contribute to the adaptive metabolic reprogram-ming in mitochondrial diseases. In addition, we emphasize the critical role of the activation of AMPK, Sirt1 and Sirt3 in the metabolicadaptation of human cells harboring mitochondrial DNA mutations.

Recent studies have revealed that AMPK and sirtuins-mediated sig-naling pathways are involved in metabolic reprogramming, which is effected by upregulation of antioxidant defense system and mito-chondrial protein acetylation, in human cells with mitochondrial dysfunction. Finally, we discuss several potential modulators of bio-energetic function such as coenzyme Q 10 , mitochondria-targeting antioxidants, resveratrol, and L-carnitine based on recent findings fromstudies on human cells and animal models of mitochondrial diseases.

Elucidation of the signaling pathway of this adaptive response tooxidative stress triggered by mitochondrial dysfunction may enable us to gain a deeper insight into the communication between mito-chondria and the nucleus and guide us to develop novel therapeutic agents for effective treatment of mitochondrial diseases.