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oai:uvadoc.uva.es:10324/700922024-12-16T09:48:15Zcom_10324_1134com_10324_931com_10324_894col_10324_1213
UVaDOC author Lavorato, Manuela author Iyer, V. Ramesh author Dewight, Williams author Cupo, Ryan R. author Debattisti, Valentina author Gomez, Ludovic author Fuente Pérez, Sergio De La author Zhao, Yan-Ting author Valdivia, Héctor H. author Hajnóczky, György author Franzini-Armstrong, Clara 2024-09-23T07:36:07Z 2024-09-23T07:36:07Z 2017 Lavorato M, Iyer VR, Dewight W, Cupo RR, Debattisti V, Gomez L, De la Fuente S, Zhao YT, Valdivia HH, Hajnóczky G, Franzini-Armstrong C. Increased mitochondrial nanotunneling activity, induced by calcium imbalance, affects intermitochondrial matrix exchanges. Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):E849-E858. doi: 10.1073/pnas.1617788113. Epub 2017 Jan 17. PMID: 28096415; PMCID: PMC5293110. 0027-8424 https://uvadoc.uva.es/handle/10324/70092 10.1073/pnas.1617788113 5 Proceedings of the National Academy of Sciences 114 1091-6490 Exchanges of matrix contents are essential to the maintenance of mitochondria. Cardiac mitochondrial exchange matrix content in two ways: by direct contact with neighboring mitochondria and over longer distances. The latter mode is supported by thin tubular protrusions, called nanotunnels, that contact other mitochondria at relatively long distances. Here, we report that cardiac myocytes of heterozygous mice carrying a catecholaminergic polymorphic ventricular tachycardia-linked RyR2 mutation (A4860G) show a unique and unusual mitochondrial response: a significantly increased frequency of nanotunnel extensions. The mutation induces Ca2+ imbalance by depressing RyR2 channel activity during excitation-contraction coupling, resulting in random bursts of Ca2+ release probably due to Ca2+ overload in the sarcoplasmic reticulum. We took advantage of the increased nanotunnel frequency in RyR2A4860G+/- cardiomyocytes to investigate and accurately define the ultrastructure of these mitochondrial extensions and to reconstruct the overall 3D distribution of nanotunnels using electron tomography. Additionally, to define the effects of communication via nanotunnels, we evaluated the intermitochondrial exchanges of matrix-targeted soluble fluorescent proteins, mtDsRed and photoactivable mtPA-GFP, in isolated cardiomyocytes by confocal microscopy. A direct comparison between exchanges occurring at short and long distances directly demonstrates that communication via nanotunnels is slower. spa Increased mitochondrial nanotunneling activity, induced by calcium imbalance, affects intermitochondrial matrix exchanges info:eu-repo/semantics/article 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URL https://uvadoc.uva.es/bitstream/10324/70092/1/Increased%20mitochondrial%20nanotunneling%20activity%2c%20induced%20by%20calcium%20imbalance%2c%20affects%20intermitochondrial%20matrix%20exchanges.pdf File MD5 0bdb8a214110f985089544710926f24c 24324713 application/pdf Increased mitochondrial nanotunneling activity, induced by calcium imbalance, affects intermitochondrial matrix exchanges.pdf