Induced pluripotent stem cells (iPSCs) hold great clinical potential for regenerative medicine. Much work has been done to investigate the mechanisms of their generation, focusing on the cell nucleus. However, the roles of specific organelles and in particular mitochondria in the potential mechanisms of nuclear reprogramming remain unclear. In this study, we sought to determine the role of mitochondrial metabolism transition in nuclear reprogramming. We found that the mitochondrial cristae had remodeled in iPSCs. The efficiency of iPSC generation was significantly reduced by down-regulation of mitochondrial inner membrane protein (IMMT), which regulates the morphology of mitochondrial cristae. Moreover, cells with the oxidative phosphorylation (OXPHOS) advantage had higher reprogramming efficiency than normal cells and the glycolysis intermediate lactic acid enhanced the efficiency of iPSCs generation. Our results show that the remodeling of mitochondrial cristae couples with the generation of iPSCs, suggesting mitochondrial metabolism transition plays an important role in nuclear reprogramming. (C) 2013 Elsevier Inc. All rights reserved.