Energetic crosstalk between organelles - Architectural integration of energy production and utilization

Cells with high and fluctuating energy demands such as cardiomyocytes need efficient systems to link energy production to energy utilization. This is achieved in part by compartmentalized energy transfer enzymes such as creat ine kinase (CK). However, hearts from CK-deficient mice develop normal card iac function under conditions of moderate workload. We have therefore inves tigated whether a direct functional interplay exists between mitochondria a nd sarcoplasmic reticulum or between mitochondria and myofilaments in cardi ac cells that catalyzes direct energy and signal channeling between organel les. We used the selective permeabilization of sarcolemmal membranes with s aponin to study the functional interactions between organelles within the c ellular architecture. We measured contractile kinetics, oxygen consumption, and caffeine-induced tension transients. The results show that in hearts o f normal mice, ATP produced by mitochondria (supplied with substrates, oxyg en, and adenine nucleotides) was able to sustain calcium uptake and contrac tile speed. Moreover, direct mitochondrially supplied ATP was nearly as eff ective as CK-supplied ATP and much more effective than externally supplied ATP, suggesting that a direct ATP/ADP channeling exists between the sites o f energy production (mitochondria) and energy utilization (sarcoplasmic ret iculum and myofilaments). On the other hand, in cardiac cells of mice defic ient in mitochondrial and cytosolic CK, marked cytoarchitectural modificati ons were observed, and direct adenine nucleotide channeling between mitocho ndria and organelles was still effective for sarcoplasmic reticulum and myo filaments. Such direct crosstalk between organelles may explain the preserv ed cardiac function of CK-deficient mice under moderate workloads.