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A highly responsive pyruvate sensor reveals pathway-regulatory role of the mitochondrial pyruvate carrier MPC

Mitochondria generate ATP and building blocks for cell growth and regeneration, using pyruvate as the main substrate. Here we introduce PyronicSF, a user-friendly GFP-based sensor of improved dynamic range that enables real-time subcellular quantitation of mitochondrial pyruvate transport, concentra...

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Autores principales: Arce-Molina, Robinson, Cortés-Molina, Francisca, Sandoval, Pamela Y, Galaz, Alex, Alegría, Karin, Schirmeier, Stefanie, Barros, L Felipe, San Martín, Alejandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077990/
https://www.ncbi.nlm.nih.gov/pubmed/32142409
http://dx.doi.org/10.7554/eLife.53917
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author Arce-Molina, Robinson
Cortés-Molina, Francisca
Sandoval, Pamela Y
Galaz, Alex
Alegría, Karin
Schirmeier, Stefanie
Barros, L Felipe
San Martín, Alejandro
author_facet Arce-Molina, Robinson
Cortés-Molina, Francisca
Sandoval, Pamela Y
Galaz, Alex
Alegría, Karin
Schirmeier, Stefanie
Barros, L Felipe
San Martín, Alejandro
author_sort Arce-Molina, Robinson
collection PubMed
description Mitochondria generate ATP and building blocks for cell growth and regeneration, using pyruvate as the main substrate. 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. 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. The functionality of the sensor in living tissue is demonstrated in the brain of Drosophila melanogaster larvae. Mitochondrial subpopulations are known to coexist within a given cell, which differ in their morphology, mobility, membrane potential, and vicinity to other organelles. 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.
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spelling pubmed-70779902020-03-19 A highly responsive pyruvate sensor reveals pathway-regulatory role of the mitochondrial pyruvate carrier MPC Arce-Molina, Robinson Cortés-Molina, Francisca Sandoval, Pamela Y Galaz, Alex Alegría, Karin Schirmeier, Stefanie Barros, L Felipe San Martín, Alejandro eLife Cell Biology Mitochondria generate ATP and building blocks for cell growth and regeneration, using pyruvate as the main substrate. 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. 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. The functionality of the sensor in living tissue is demonstrated in the brain of Drosophila melanogaster larvae. Mitochondrial subpopulations are known to coexist within a given cell, which differ in their morphology, mobility, membrane potential, and vicinity to other organelles. 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. eLife Sciences Publications, Ltd 2020-03-06 /pmc/articles/PMC7077990/ /pubmed/32142409 http://dx.doi.org/10.7554/eLife.53917 Text en © 2020, Arce-Molina et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Arce-Molina, Robinson
Cortés-Molina, Francisca
Sandoval, Pamela Y
Galaz, Alex
Alegría, Karin
Schirmeier, Stefanie
Barros, L Felipe
San Martín, Alejandro
A highly responsive pyruvate sensor reveals pathway-regulatory role of the mitochondrial pyruvate carrier MPC
title A highly responsive pyruvate sensor reveals pathway-regulatory role of the mitochondrial pyruvate carrier MPC
title_full A highly responsive pyruvate sensor reveals pathway-regulatory role of the mitochondrial pyruvate carrier MPC
title_fullStr A highly responsive pyruvate sensor reveals pathway-regulatory role of the mitochondrial pyruvate carrier MPC
title_full_unstemmed A highly responsive pyruvate sensor reveals pathway-regulatory role of the mitochondrial pyruvate carrier MPC
title_short A highly responsive pyruvate sensor reveals pathway-regulatory role of the mitochondrial pyruvate carrier MPC
title_sort highly responsive pyruvate sensor reveals pathway-regulatory role of the mitochondrial pyruvate carrier mpc
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077990/
https://www.ncbi.nlm.nih.gov/pubmed/32142409
http://dx.doi.org/10.7554/eLife.53917
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