SR and mitochondria: Calcium cross-talk between kissing cousins

► Mitochondrial Ca2 + activates Krebs cycle enzymes to adapt energy supply to demand. ► Close association of mitochondria to SR establishes a Ca2 + microdomain. ► Mitofusin 2, but not mitofusin 1 tethers mitochondria to the SR in cardiac myocytes. ► Impaired mitochondrial Ca2 + uptake causes energetic mismatch and oxidative stress.