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Introduction: Elucidating the mechanisms that link fiber contraction with ATP synthesis is important to understand skeletal muscle function. Mitochondria exhibit a particular architecture in skeletal muscle fibers. A large fraction resides along the I band, in close proximity to myofibrils where ATP production is essential for contraction, and closely interact with the triad structures. Sub-sarcolemmal mitochondria have a different distribution, and contain different components of the metabolic protein complexes. Objective: We studied mitochondrial Ca2 transients following depolarization by potassium (or electrical stimulation) of single skeletal muscle fibers, and their relation with metabolic output and membrane potential changes in mitochondria. Results: In isolated muscle fibers from FBD muscle, depolarization increased both cytoplasmic and mitochondria Ca2 levels. Mitochondrial Ca2 uptake required functional IP3R and RyR1 channels. Moreover, inhibition of either one decreased basal O2 consumption rate but only RyR1 inhibition decreased ATP-linked O2 consumption. Depolarization-induced Ca2 signals in sub-sarcolemmal mitochondria were accompanied by a reduction in mitochondria membrane potential; Ca2 signals propagated towards intermyofibrillar mitochondria, where mitochondrial membrane potential increased. Likewise, oligomycin induced propagation of mitochondria membrane potential from the surface towards the center of the fiber. Results are compatible with Ca2 -dependent propagation of mitochondrial membrane potential from the surface towards the center of the fiber. Conclusion: Ca2 -dependent propagation of mitochondrial membrane potential from the surface towards the center of the fiber could have a critical role in control of mitochondria metabolism both at rest and after depolarization as part of an "excitation-metabolism" coupling in skeletal muscle fibers.