In mammalian skeletal muscle, an intimate association between the sarcoplasmic reticulum (SR) and mitochondria results in a symbiotic and privileged bidirectional communication between these organelles. Orthograde signaling reflects SR calcium (Ca) release stimulating mitochondrial adenosine triphosphate production via excitation-metabolism coupling. Retrograde signaling involves mitochondrial inhibition of local SR Ca release by controlling the redox environment of the Ca release unit.