![]() ![]() Mitochondria are the chief energy generators of animal cells, accounting for over 90% of ATP production, and they also generate building blocks for the synthesis of sugars, amino acids, nucleic acids and prosthetic groups, essential elements for tissue growth, plasticity and regeneration. ![]() The present tool can be used to investigate how mitochondrial diversity relates to metabolism, to study the role of MPC in disease, and to screen for small-molecule MPC modulators. Mitochondrial subpopulations are known to coexist within a given cell, which differ in their morphology, mobility, membrane potential, and vicinity to other organelles. The functionality of the sensor in living tissue is demonstrated in the brain of Drosophila melanogaster larvae. We report that cultured mouse astrocytes maintain mitochondrial pyruvate in the low micromolar range, below cytosolic pyruvate, which means that the mitochondrial pyruvate carrier MPC is poised to exert ultrasensitive control on the balance between respiration and anaplerosis/gluconeogenesis. Here we introduce PyronicSF, a user-friendly GFP-based sensor of improved dynamic range that enables real-time subcellular quantitation of mitochondrial pyruvate transport, concentration and flux. Mitochondria generate ATP and building blocks for cell growth and regeneration, using pyruvate as the main substrate. ![]()
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