Hypoxia-induced NAD⁺ interventions promote tumor survival and metastasis by regulating mitochondrial dynamics

Hypoxia, an important feature of the tumor microenvironment, is responsible for the chemo-resistance and metastasis of malignant solid tumors. Recent studies indicated that mitochondria undergo morphological transitions as an adaptive response to maintain self-stability and connectivity under hypoxic conditions. NAD⁺ may not only provide reducing equivalents for biosynthetic reactions and in determining energy production, but also functions as a signaling molecule in mitochondrial dynamics regulation. In this review, we describe the upregulated KDAC deacetylase expression in the mitochondria and cytoplasm of tumor cells that results from sensing the changes in NAD⁺ to control mitochondrial dynamics and distribution, which is responsible for survival and metastasis in hypoxia.