Studies with transgenic animal and cell models or human samples demonstrated various proteins that may interact with NRF2-KEAP1 axis under normal physiologic and pathologic conditions to promote NRF2-mediated mitochondrial bioenergetics. NRF2-KEAP1 axis may communication or compete with SIRT1, PI3K/Akt, DJ-1, and/or p62 to liberate NRF2 from KEAP1 for antioxidant response element (ARE)-mediated transcriptional activation of genes involved in mitochondrial energy metabolism, biogenesis, and quality control as described in Table 1. Aktl, serine/threonine-specific protein kinase; DJ-1, protein deglycase (or Parkinson disease protein 7, PARK7); KEAP1, Kelch-like ECH-associated protein 1; p62, ubiquitin-binding protein (or sequestosome 1, SQSTM1); PGAM5, PGAM family member 5, mitochondrial serine/threonine protein phosphatase; PI3K, phosphoinositide 3-kinase; SIRT1, sirtuin 1; sMaf, small musculoaponeurotic fibrosarcoma (MafF, MafG, MafK).